AUGUST 2023 | VOLUME 25 | ISSUE 8

Emergency Medicine Practice Evidence-Based Education • Practical Application

CLINICAL CHALLENGES:
• What are the clinical risk factors
for pulmonary embolism?
• How are patients assessed
for probability of pulmonary
embolism?
• What are the highest-value
diagnostic tests for detecting a
pulmonary embolism?

Authors
Alfred Sacchetti, MD, FACEP
Director of Clinical Services, Emergency
Department, Virtua Our Lady of Lourdes
Hospital, Camden, NJ; Assistant Clinical
Professor of Emergency Medicine, Thomas
Jefferson University, Philadelphia, PA

Michael Driscoll, DO, FACOI, FCCP

Attending Physician, Department of Medicine, Evidence-Based
Section of Pulmonary and Critical Care, Virtua
Our Lady of Lourdes Medical Center, Camden, Management of
Pulmonary Embolism in
NJ

Peer Reviewers the Emergency Department

Mark Andreae, MD
Assistant Professor of Surgery and Emergency
Medicine, Institute for Critical Care Medicine,
Icahn School of Medicine at Mount Sinai, New
York, NY
Christopher Willoughby, MD,
FAAEM
Assistant Professor of Clinical Medicine,
Department of Emergency Medicine, Louisiana
State University Health Sciences Center New
Orleans, New Orleans, LA
Prior to beginning this activity, see “CME
Information” on page 2.
n Abstract
Patients with pulmonary emboli present both diagnostic and
therapeutic challenges to the emergency clinician, because
initial symptoms can be variable and overlap with other medical
conditions. This issue reviews treatment options for patients
with pulmonary emboli based on risk stratification scores of low,
intermediate-low, intermediate-high, and high risk classifications.
The evidence on laboratory testing and imaging is presented,
as well as treatment strategies that include anticoagulation,
thrombolytics, and mechanical or surgical thrombectomy.
Management decisions regarding pregnancy and COVID-19 are
discussed, as well as considerations for outpatient treatment of
low-risk patients.

For online For mobile

access: app access:

This issue is eligible for CME credit. See page 2. EBMEDICINE.NET

 CME Information
Date of Original Release: August 1, 2023. Date of most recent review: July 10, 2023. Termination date: August 1, 2026.
Accreditation: EB Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide
continuing medical education for physicians.
Credit Designation: EB Medicine designates this enduring material for a maximum of 4 AMA PRA Category 1 CreditsTM. Physi-
cians should claim only the credit commensurate with the extent of their participation in the activity.
Specialty CME: Not applicable. For more information, contact Customer Service at 678-366-7933.
ACEP Accreditation: Emergency Medicine Practice is approved by the American College of Emergency Physicians for 48 hours of ACEP Cat-
egory I credit per annual subscription.
AAFP Accreditation: The AAFP has reviewed Emergency Medicine Practice, and deemed it acceptable for AAFP credit. Term of approval is from
07/01/2023 to 06/30/2024. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This session,
Evidence-Based Management of Pulmonary Embolism in the Emergency Department is approved for 4.0 enduring material AAFP Prescribed
credits.
AOA Accreditation: Emergency Medicine Practice is eligible for 4 Category 2-B credit hours per issue by the American Osteopathic Association.
Needs Assessment: The need for this educational activity was determined by a practice gap analysis; a survey of medical staff, including the
editorial board of this publication; review of morbidity and mortality data from the CDC, AHA, NCHS, and ACEP; and evaluation responses from
prior educational activities for emergency physicians.
Target Audience: This enduring material is designed for emergency medicine physicians, physician assistants, nurse practitioners, and residents.
Goals: Upon completion of this activity, you should be able to: (1) identify areas in practice that require modification to be consistent with current
evidence in order to improve competence and performance; (2) develop strategies to accurately diagnose and treat both common and critical ED
presentations; and (3) demonstrate informed medical decision-making based on the strongest clinical evidence.
CME Objectives: Upon completion of this activity readers will be able to: (1) identify the risks of a pulmonary embolism based on a patient's
clinical presentation; (2) select appropriate diagnostic studies to identify the presence of a pulmonary embolism; (3) select appropriate diagnostic
studies to determine the severity of the patient’s condition; and (4) develop a management approach based on the clinical and diagnostic charac-
teristics of the patient.
Discussion of Investigational Information: As part of the activity, faculty may be presenting investigational information about pharmaceutical
products that is outside Food and Drug Administration approved labeling. Information presented as part of this activity is intended solely as
continuing medical education and is not intended to promote off-label use of any pharmaceutical product.
Disclosure: It is the policy of EB Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME activities.
All individuals in a position to control content have disclosed all financial relationships with ACCME-defined ineligible companies. EB Medicine
has assessed all relationships with ineligible companies disclosed, identified those financial relationships deemed relevant, and appropriately
mitigated all relevant financial relationships based on each individual’s role(s). Please find disclosure information for this activity below:
Planners Faculty
• Daniel J. Egan, MD (Course Director): Nothing to Disclose • Alfred Sacchetti, MD (Author): Nothing to Disclose
• Andy Jagoda, MD (Editor-in-Chief): • Michael Driscoll, DO (Author): Nothing to Disclose
l Pfizer (Consultant/Advisor) • Mark Andreae, MD (Peer Reviewer): Nothing to Disclose
l Janssen (Consultant/Advisor) • Christopher Willoughby, MD (Peer Reviewer): Nothing to Disclose
l Abbott Laboratories (Consultant/Advisor) • Aimee Mishler, PharmD (Pharmacology Editor): Nothing to Disclose
• Kaushal Shah, MD (Associate Editor-in-Chief): Nothing to Disclose • Joseph D. Toscano, MD (Research Editor): Nothing to Disclose
• Dorothy Whisenhunt, MS (Content Editor): Nothing to Disclose
• Cheryl Belton, PhD (Content Editor): Nothing to Disclose

Commercial Support: This issue of Emergency Medicine Practice did not receive any commercial support.
Earning CME Credit: Go online to https://www.ebmedicine.net/CME and click on the title of the test you wish to take. When completed, a CME
certificate will be emailed to you.
Additional Policies: For additional policies, including our statement of conflict of interest, source of funding, statement of informed consent, and
statement of human and animal rights, visit https://www.ebmedicine.net/policies

CEO: Stephanie Williford

Director of Finance & Analytics: Robin Wilkinson
Publisher: Suzanne Verity
Director of Editorial Quality: Dorothy Whisenhunt, MS
Senior Content Editor: Cheryl Belton, PhD, ELS
Direct all inquiries to: Managing Editor: Angie Wallace
Phone: 678-366-7933 CME & Content Coordinator: Kristen Raynor, MEd
Fax: 770-500-1316 Education Coordinator: Kandis Slater
5600 Spalding Drive, Unit 921697 Customer Service Representative: Katie Resumovic
Norcross, GA 30010-1697 Account Executive: Dana Stenzel
Director of Marketing: Anna Motuz, MBA
E-mail: ebm@ebmedicine.net Email Marketing Specialist: Joshua Devou, MBA
Website: www.ebmedicine.net Marketing Specialist: Valerie Yuhouse
Database Administrator: Jose Porras

ISSN info and disclaimer:

Emergency Medicine Practice (ISSN Print: 1524-1971, ISSN Online: 1559-3908, ACID-FREE) is published monthly (12 times per year) by EB Medicine
(5600 Spalding Drive, Unit 921697, Norcross, GA 30010-1697). Opinions expressed are not necessarily those of this publication. Mention of products
or services does not constitute endorsement. This publication is intended as a general guide and is intended to supplement, rather than substitute,
professional judgment. It covers a highly technical and complex subject and should not be used for making specific medical decisions. The materials
contained herein are not intended to establish policy, procedure, or standard of care. Copyright © 2023 EB Medicine. All rights reserved. No part of
this publication may be reproduced in any format without written consent of EB Medicine. This publication is intended for the use of the individual
subscriber only and may not be copied in whole or part or redistributed in any way without the publisher’s prior written permission.

AUGUST 2023 • www.ebmedicine.net 2 ©2023 EB MEDICINE

 Case Presentations
An obese 55-year-old man reports exertional dyspnea that began 2 days prior…
• The man says he is generally active, despite being obese, and says that he walks extensively for his job.
CASE 1

• His ECG is normal sinus rhythm at 95 beats/min and his resting pulse oximetry is at 94%. There are no
other abnormalities. Chest x-ray, natriuretic peptide, and high-sensitivity troponin are normal.
• All of his symptoms can be explained by his weight, but you wonder whether you should start down a
diagnostic pulmonary embolism algorithm...

A 65-year-old woman presents with a complaint of shortness of breath she developed that morning…
• She says she recently recovered from COVID-19 disease and was doing well prior.
CASE 2

• On examination, her lungs have a few residual ronchi from her illness, but are otherwise clear. Vital signs
are normal, and her pulse oximetry is 97% on room air. As part of her workup, a D-dimer is ordered and
returns incalculably high. She has a well-documented IV contrast allergy. A pulmonary perfusion scan
was ordered, which shows a clear perfusion defect consistent with a pulmonary embolism.
• You consider whether this patient is a candidate for outpatient treatment and which medications to use...

A 60-year-old woman presents in extremis via basic EMS…

• She was recently released from the hospital following a 1-week hospitalization for COVID-19 disease,
during which she was placed on low-molecular-weight heparin (LMWH). She stopped the LMWH 4 days
CASE 3

prior. She said she developed severe shortness of breath about 1 hour ago when she stood up from a
recliner she had been resting in.
• On arrival to the ED, she was cyanotic, tachypneic, tachycardic, and verbalizing “I can’t breathe”
repeatedly. Initial pulse oximetry was 70%, with a sinus tachycardia of 130 beats/min and a blood
pressure of 84/40 mm Hg.
• Does this patient require endotracheal intubation, and should thrombolytics be started immediately?

n Introduction n Critical Appraisal of the Literature

The presentation of patients with pulmonary emboli
ranges from the patently obvious to the extremely
subtle. Clinical outcomes may seem, at times, to defy
any physiologic management. Patients with massive
clot burden may survive with no complications follow-
ing minimal interventions while others with relatively
minor emboli may die despite aggressive care.
Venous thromboembolism (VTE) is among the
most lethal of all acute medical conditions. Un-
treated VTE has an acute mortality of 25%, which can
decrease to 5% with timely medical management.
Nonetheless, even with appropriate care, approxi-
mately 15% to 30% of patients who are treated for a
pulmonary embolism will die within 90 days.1-3 The
cause of death may not be the pulmonary embolism
itself, but the underlying medical pathology that led
to the offending clot. Misdiagnosis of patients who
were discharged from the ED but were ultimately
diagnosed with pulmonary emboli occurs in 11.9% to
19% of cases,4 and pulmonary embolism remains the
third most common cause of death from cardiovascu-
lar causes. This issue of Emergency Medicine Practice
presents an emergency medicine approach to the
diagnosis, treatment, and disposition of patients with
pulmonary emboli.
A literature search was performed using multiple
databases including PubMed, Google Scholar,
Emergency Medical Abstracts, MEDLINE®, and the
Cochrane Database of Systematic Reviews, with
no time criteria. Search terms included pulmonary
embolism with the following subtitles: diagnosis,
laboratory, radiography, ultrasound, physical
examination, risk factors, stratification, thrombolysis,
anticoagulation, and invasive, with no restrictions on
the type of article. Over 500 articles were identified,
of which 141 were selected. A large number of
descriptive studies were identified, along with
anecdotal therapeutic reports. High-quality subject
reviews with evidence-based recommendations on
diagnostic and therapeutic approaches to pulmonary
embolism, along with specialty society guidelines and
policy and procedures were also reviewed, and 99
were identified for inclusion in this manuscript.
n Etiology and Pathophysiology
Clot formation occurs continuously in the venous sys-
tems of the body. These clots tend to be very small,
and they are broken down by the action of circulat-
ing enzymes, most prominently, plasmin. Pathologic

AUGUST 2023 • www.ebmedicine.net 3 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.

deep vein thrombi may be described as venous clots
that do not resolve spontaneously but instead propa-
gate, resulting in obstruction or migration. The most
common conditions leading to venous thrombus
formation were described by Virchow, in which he
listed in his triad of (1) vessel wall injury, (2) venous
stasis, and (3) hypercoagulability. Vessel wall injuries
denude the endothelium, leading to exposure of the
underlying thrombogenic media layers of the vessel.
Venous stasis leads to thrombus formation in the cusp
of the venous valves, where prolonged contact with
platelets allows for activation of other components of
the clotting cascade. Hypercoagulability may result
from inborn errors in the coagulation cascade, the
presence of mucus-secreting tumors, or iatrogenic
thrombotic medications or devices.3,5
Once formed, venous clots can follow 1 of 3
pathways. First, they may be lysed by the body’s
normal thrombolytic processes. Second, they may
propagate and become larger, leading to further
clot formation and obstruction in the affected vessel.
Finally, they may break free and migrate to a more
proximal portion of the venous tree, including the
lungs. By definition, any material migrating to the
pulmonary arterial system is termed a pulmonary
embolism, including air, amniotic fluid, and foreign
bodies, although blood clots are, by far, the most
common source of pulmonary emboli and will be the
focus of this discussion.
When an embolism lodges in the pulmonary
vascular tree, it produces a cascade of mechanical
and chemical reactions. Prominent among the
mechanical reactions is obstruction of flow to the
portions of the lung distal to where the embolus is
embedded. A decrease in the available surface area
for exchange of oxygen and carbon dioxide occurs
in alveoli supplied by that portion of the pulmonary
arterial circulation. If the clot is large enough,
pulmonary hypertension may result. The right
ventricle is anatomically and physiologically designed
to pump blood into a low-pressure system, and acute
pulmonary hypertension leads to right ventricular
dilation and pulmonary vascular congestion. This
may translate to depressed blood flow from both
the superior and inferior vena cavas through the
tricuspid valve. As right ventricular pressures increase,
displacement of the intraventricular septum into the
left ventricle occurs, affecting left ventricular function
as well. The mechanical obstruction of the pulmonary
circulation will decrease pulmonary venous return to
the left side of the heart. If significant enough, this
leads to physiologic hypovolemia and shock. Right
ventricular dysfunction secondary to clot mass does
not occur until approximately 50% of the pulmonary
vascular tree is embolized.3,6
Compounding these problems is the ability of
fresh emboli to propagate within the pulmonary
circulation itself. As with clots anywhere in the circu-
AUGUST 2023 • www.ebmedicine.net
latory system, pulmonary emboli activate the clot-
ting cascade, damage the endothelium, and lead to
localized blood stagnation. The presence of a fresh
clot in the pulmonary arteries leads to the release of
a number of vasoactive chemicals that contribute to
pulmonary hypertension. Most prominent of these are
the endothelins: serotonin, thromboxane A2, adenos-
ine, and multiple prostaglandins, along with other
small molecules. The presence of these agents leads
to competing actions of vasoconstriction and vasodi-
lation in the pulmonary arteries; however, the overall
effect is strongly weighted toward vasoconstric-
tion. Because of the soluble nature of these agents,
vasoactive effects occur in both the embolized and
nonembolized portions of the lungs.1,3,6 Pulmonary
infarctions may occur in 16% to 31% of patients with
pulmonary emboli.2,7
Pulmonary emboli do not occur as isolated
events. Frequently, more than one embolism will
occur in any given patient. It is often said that it is
not the pulmonary embolism you diagnose that kills
the patient, but the subsequent ones that originate
from the offending clot source. Although not proven,
it may be that the pulmonary vasculature has been
primed by the initial clot and the second offending
clot is able to exert a larger vasoactive effect, which
leads to the cardiovascular collapse.
Risk Factors for Pulmonary Emboli
Most of the risk factors for pulmonary emboli are
similar to risk factors for the formation of deep
venous thrombi, although they are not identical.8 Any
circumstances that lead to venous stasis, particularly
in the lower extremities, are considered risk factors
for a pulmonary emboli. Extended bed rest of any
duration places patients at risk for development of
deep vein thrombosis (DVT). With limited activity,
even young patients can develop clots in the
lower extremities. Compression devices, as well as
anticoagulants, can limit the formation of thrombi.
However, clinicians should still consider the possibility
of a blood clot in patients despite the use of DVT
prophylaxis or treatments.
Direct trauma to an extremity, even without
creation of a fracture, produces soft-tissue edema and
micro-clots. If severe enough, such clotting can lead
to propagation and DVT.8
Proximal obstruction to blood flow through a
vein can lead to stasis and clot formation. Pathologic
masses such as tumors, excessive adipose tissue, and
indwelling foreign bodies such as vascular devices
can all serve as a nidus for clot formation. The clots
distal to the offending source of obstruction generally
do not migrate to the lungs, as they are blocked by
the obstruction. However, these clots can serve as the
nidus that allows propagation of a clot more proxi-
mally, which can then embolize to the lungs.1,2
Hypercoagulable states are independent risk
4 ©2023 EB MEDICINE
factors for thromboembolic events. Cancer of any
type is a risk factor for pulmonary embolism, account-
ing for up to 66.7% of deaths in oncology patients.9
All tumors place patients at risk for thromboembolic
events, but those that contain mucinous secreting
cells are the most common.8,10,11 Pancreatic, colonic,
and lung are the most common of these types of can-
cers. Cancer patients with pulmonary emboli can also
present differently from those without cancer. Overall,
they are older, with an average age 64 years versus
58 years of age, and they are less likely to present
with chest pain, 18% versus 37%.12
Hypercoagulable states related to genetic fac-
tors can occur in up to 30% of VTE patients. The vast
majority of these abnormalities are related to factor V
Leiden and prothrombin G2021A mutations. Patients
may be heterozygous or homozygous for the abnor-
mal enzymes and vary in their severity for the forma-
tion of pathologic clots.10
General anesthesia is an independent risk factor
for thrombus formation. Patients with a history
of recent surgery, even procedures not involving
the lower extremities, have a lower threshold for
abnormal clotting.1
In the Prospective Investigation of Pulmonary
Embolism Diagnosis II (PIOPED II) study, the most
common risk factors found included: female sex (58%
of patients), followed by immobilization (25%), recent
surgery (21%), malignancy (19%), and travel >4 hours
in the previous month (12%).13,14 Table 1 lists com-
mon risk factors for pulmonary emboli.
n Differential Diagnosis
Based on the clinical presentation of patients with
pulmonary emboli, the differential diagnosis is quite
extensive. Certainly, myocardial ischemia should be
considered in patients with chest pain. In addition,
primary pulmonary pathology including chronic
obstructive pulmonary disease (COPD), asthma,
pneumonia, pneumothorax, and pleuritis all need to
be considered. Fortunately, many of the diagnostic
studies used to evaluate patients for pulmonary
Table 1. Clinical Risk Factors for
Pulmonary Embolism1,13,14
• Female sex/estrogen therapy
• Prolonged immobility (≥3 days)
• General anesthesia/recent surgery
• Cancer
• Travel ≥4 hours
• Major trauma/fracture
• Pacemaker placement
• Venous catheterization
• Obesity
• Antiphospholipid syndrome
• Chronic inflammatory disorders
• Heparin-induced thrombocytopenia
AUGUST 2023 • www.ebmedicine.net
emboli are helpful in excluding other diagnoses in
their differential.
Patients with primary cardiovascular presenta-
tions including chest pain, shortness of breath, and
hemoptysis will commonly be considered for the
possibility of pulmonary emboli. Patients with non-
pulmonary presentations including syncope, weak-
ness, malaise, and other nonspecific complaints may
also be considered for pulmonary emboli, depending
on the clinical circumstances involved. Underlying
conditions such as COPD, congestive heart failure,
and other chronic conditions should increase the clini-
cians’ suspicion for this disease. Syncope in conjunc-
tion with other risk factors may lead to the consider-
ation of pulmonary emboli, although isolated syn-
cope with no other associated symptoms suggestive
of a pulmonary embolism is not an indication for an
evaluation for thromboembolic disease. A prospec-
tive study of 1380 syncope patients found a pulmo-
nary embolism at presentation in only 19 patients.15
A retrospective cohort study of 224 patients found a
pulmonary embolism in 22 patients; however, all had
classic signs and symptoms of the disease.16
Misdiagnosis of patients discharged from the
ED but ultimately diagnosed with pulmonary emboli
occurs in 11.9% to 19% of pulmonary embolism
patients. A delayed diagnosis in patients admitted to
the hospital can be as high as 21.5%.4 Patients with
pulmonary emboli missed on their initial ED visits
tended to be older, 77.5 years of age versus 67 years
of age; have less dyspnea, 45.5% versus 59.9%; less
chest pain, 18% versus 49.5%; and more nonspecific
symptoms, 29.5% versus 8.8%. Morbidity and
mortality can be as high as 30% to 43% in patients
with a missed pulmonary embolism diagnosis,
compared to 1.6% in those diagnosed initially.17
n Prehospital Care
For patients who have complaints suggestive of pul-
monary embolism and are transported by an emergen-
cy medical services (EMS) system, standard prehospital
chest pain or shortness of breath protocols are ap-
propriate. There is little that traditional prehospital
intervention has to offer pulmonary embolism patients
aside from supplemental oxygen and cardiac monitor-
ing. Airway interventions and positive-pressure ventila-
tion have significant physiologic effects on patients
with large pulmonary emboli and should be used
according to prevailing EMS protocols for patients with
hypoxia and/or respiratory distress.
n Emergency Department Evaluation
History
Most patients with pulmonary emboli will present
with complaints of either dyspnea or chest pain. For
those presenting with dyspnea, the time of onset and
5 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.
duration of symptoms can help distinguish pulmonary
embolism-related dyspnea from that of congestive
heart failure, pneumonia, and COPD.
Data from the PIOPED II study found that dyspnea
is the most common presenting symptom for patients
with a pulmonary embolism, occurring in 79% of indi-
viduals. Dyspnea at rest occurred in 61% of patients,
while dyspnea only with exertion was found in 13% to
18%. In 41%, the onset of dyspnea was rapid; in most
cases occurring within seconds, and within minutes
in another 26%.13 Similarly, patients with chest pain
should be asked for a description of their symptom
characteristics. In the same PIOPED II study, pleuritic
chest pain occurred in 47% of patients, with non–pleu-
ritic chest pain in another 17%.13
If pulmonary embolism is considered high on
the differential, ask specifically about lower extremity
symptoms, as swelling or pain in the legs may be
present in 39% to 42% of patients.13 Asking specific
questions concerning the risk factors listed in Table 1
(page 5) can also help establish or refute a pulmonary
embolism as the source of a patient’s symptoms.
Physical Examination
Vital Signs
From a clinical perspective, the most important
point to remember regarding the ED presentation
of pulmonary embolism patients is that vital signs
are often normal. According to PIOPED II, the most
common vital sign abnormalities in patients with
pulmonary embolism were tachypnea (52%-57%) and
tachycardia (21%-28%).13 A resting heart rate of >100
beats/min occurred in 26% of patients in the PIOPED
II study.13 A normal heart rate does not eliminate
the possibility of a thromboembolic event, nor does
reversion of an elevated heart rate to normal, which
may be seen in 18% of patients.18
Abnormal respiratory rates are less predictive
of pulmonary emboli, although at the extreme, it
is predictive of severe disease. Respiratory rates
>30 breaths/min demonstrated a sensitivity of 43%
and a specificity of 69% for pulmonary embolism-
related deaths. Tachypnea with a respiratory rate
>20 breaths/min was found in 57% of patients in the
PIOPED II study.13,19
Hypotension is the least specific vital sign, oc-
curring in 5% of pulmonary embolism patients. Intui-
tively, it would seem that the size of the clot burden
would correlate with the presence of hypotension.
However, because of the vasoactive actions of the
clots in the pulmonary circulation, even small clots
can produce hypotension. Conversely, large clots
may have no impact on blood pressure.20
Other Physical Examination Findings
In 22% of patients with pulmonary embolism,
abnormalities in the cardiac examination can be
found, but aside from tachycardia, they are not easily
AUGUST 2023 • www.ebmedicine.net
characterized.13 Pleuritic chest pain was found in 35%
to 46% of these patients, while non–pleuritic pain was
present in 18% to 20%.13 Other studies found similar
results when signs, symptoms, and risk factors were
examined.14,21
There is variability in presentations according
to patients’ age. Patients aged <65 and >85 years
presented with a similar frequency of dyspnea,
occurring in 77% and 74%, respectively. However,
chest pain showed a significant age difference, being
present in 60% of those aged <65 years but in only
31% of those aged >85 years. Tachycardia was found
in 19% of those aged <65 years but in 11.4% in those
aged >85 years. Other clinical signs and symptoms
were similar in both the younger and older patients.21
Visual cyanosis reinforces the impression of
severe dyspnea, regardless of etiology. The presence
of 3 to 5 g/dL of deoxygenated hemoglobin is
generally enough to produce a bluish discoloration of
the skin.22 In a person with normal hemoglobin levels,
cyanosis will appear at a pulse oximetry reading of
approximately 85%.22 Pulse oximetry can indicate
unrecognized hypoxemia; however, the degree
of hypoxemia is extremely variable and does not
correlate with the clot load in the pulmonary vascular
tree. An oxygen saturation of <90% has only a 32%
sensitivity for the diagnosis of pulmonary embolism.
However, pulse oximetry does correlate with short-
term mortality, with a death rate of 16.7% for patients
with baseline pulse oximetry <88% compared to 4.8%
for those with pulse oximetry ≥88%.19 Part of this
variability stems from the ability of even small clots
to induce significant shunting and vasoconstriction. A
low pulse oximetry reading should raise concern for
a possible pulmonary embolism; however, a normal
reading should not reassure a clinician that the
disease does not exist.
Auscultation of the lungs is helpful in identifying
other pathology rather than confirming a pulmonary
embolism. In the PIOPED II study, rales were found in
21% of patients, wheezing in 6%, and ronchi in 5%.13
Splinting secondary to nontraumatic chest pain
indicates some form of pleuritic or musculoskeletal
irritation as the source of pain, but is not specific
to pulmonary emboli, occurring in only 17% of
patients.13,23 If the pleural inflammation is secondary
to an infarction of the lung, it will generally take
time to develop and will not be useful as an acute
screening finding.
Jugular venous distention can be seen in up to
11% of pulmonary embolism patients but can occur in
other disease states such as congestive heart failure,
primary pulmonary hypertension, and right-sided
valvular disease.13,23
Lower extremity edema, swelling, or tenderness
are common findings in DVT. Since lower extrem-
ity veins are the most common source of pulmonary
emboli, there is a strong association between physical
6 ©2023 EB MEDICINE
findings of DVT and pulmonary embolism, and it may utilized to determine the need for further diagnostic
be seen in up to 39% to 56% of patients. However, testing. These clinical probability scoring systems
the absence of lower extremity clots does not exclude are not the same as the outcome and management
a pulmonary clot. Regardless, it is important to in- scoring systems discussed in ”Risk Stratification
clude a lower extremity examination in the evaluation Categorization“ section, on page 11.
of patients with suspected pulmonary embolism.24
Migration of venous thrombi from the upper
Online calculators for these scores are
extremities to the lungs is much less common,
available at www.MDCalc.com
occurring in <4.8% of cases. The diagnosis of upper
• Wells’ Criteria for Pulmonary
extremity DVT includes internal jugular and subclavian
Embolism: www.mdcalc.com/calc/115/
clots and is not restricted to just the arms.24
wells-criteria-pulmonary-embolism
• Geneva Score (Revised) for Pulmonary
Diagnostic Risk Scoring Systems
Embolism: www.mdcalc.com/calc/1750/
No single sign or symptom is completely reliable in
geneva-score-revised-pulmonary-embolism
confirming or excluding the diagnosis of pulmonary
• PERC Rule for Pulmonary Embolism: www.
embolism. Clinical gestalt alone demonstrates poor
mdcalc.com/calc/347/perc-rule-pulmonary-
performance in excluding the need for further testing
embolism
in potential pulmonary embolism patients, with a
• YEARS Algorithm for Pulmonary Embolism
kappa between clinicians examining the same patient
(including adaptation for pregnant patients):
as low as 0.33.25,26 To compensate for this problem,
www.mdcalc.com/calc/4067/years-algorithm-
different components of patient presentations and
for-pulmonary-embolism-pe
diagnostics have been combined into pulmonary
embolism scoring systems to generate clinical
pretest probabilities. Table 2 contains a summary
of different validated clinical pretest probabilities n Diagnostic Studies
scoring systems. Although there are minor variations Because of the variable clinical presentations in
among systems, in general, all of them divide patients with pulmonary emboli, diagnostic studies
the risk for pulmonary embolism into low (5%- play a major role in the diagnosis of this disease. Any
10%), intermediate (25%-30%) or high (60%-65%) diagnostic studies used to evaluate for a pulmonary
probabilities. The clinical risk categorization is then embolism must be interpreted in conjunction with

Table 2. Clinical Pretest Probability Scoring Systems

Criteria Scoring System
Wells rGeneva PERC YEARS
Age (years) >65: 1 ≥50: 1
Surgery or immobilization within the past 4 weeks 1.5 2 1

Cancer 1 2
Previously diagnosed PE or DVT 1.5 3 1
Hormonal estrogenic treatment 1
Hemoptysis 1 2 1 1
Clinical signs of DVT 3 1
Unilateral lower limb pain 3
Pain on lower limb deep vein palpation and unilateral edema 4 1

Heart rate (beats/min) >100: 1.5 75-94: 3 ≥100: 1

≥95: 5
Pulse oxygen saturation <95% 1
PE is #1 diagnosis or equally likely 3 1
Clinical Probability
Very low (exclusion threshold) 0
Low PE risk (5%-10%) 0-1 0-3 0
Intermediate PE risk (25%-30%) 2-6 4-10 ≥1
High PE risk (60%-65%) ≥7 ≥11 1

Abbreviations: DVT, deep vein thrombosis; PE, pulmonary embolism; PERC, pulmonary embolism rule-out criteria; VTE, venous thromboembolism.
www.ebmedicine.net

AUGUST 2023 • www.ebmedicine.net 7 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.

the patient’s clinical pretest probability for having a
pulmonary thrombus.
Electrocardiogram
ECG may be useful, but it is not diagnostic, with
approximately 25% of patients having normal
tracings.27 A resting tachycardia is the most common
ECG finding in pulmonary embolism patients, seen
in 26% to 27% of cases. The triad of an S wave in
lead 1 in conjunction with Q waves and inverted
T wave in lead 3 (S1Q3T3) is neither sensitive nor
specific. Although historically described as diagnostic
for pulmonary embolism, more rigorous studies
have proven that only 3.7% of pulmonary embolism
patients do have these findings.13,27 Other ECG
abnormalities found in patients with acute pulmonary
embolism include right ventricular strain, as defined
by simultaneous T-wave inversions in the inferior and
right precordial leads (11.1%), atrial dysrhythmias
(10.1%), and right bundle branch block (9%). Atrial
fibrillation is the most common arrhythmia found in
acute pulmonary embolism patients, but it is not an
independent predictor of a pulmonary blood clot.27,28
Laboratory Studies
D-dimer Assay
A D-dimer study analyzes the presence of fibrinogen
split products that result from the fibrinolysis of a
blood clot. More specifically, these tests identify
the presence of the 2 bound fibrin D-domains
created by the action of factor XIII. The physiologic
baseline for D-dimer levels varies with age, and is
up to 2.5 times higher in patients aged >70 years
compared with those aged <50 years. Levels also
change with the duration of the clot, dropping
significantly in patients with clots older than 7 days.29
There are over 30 different assays and 20 different
monoclonal antibodies used in D-dimers. Each assay
has a threshold above which a test is considered
positive. The most sensitive and reliable tests are
the enzyme-linked immunosorbent assays (ELISAs)
and the enzyme-inked immunofluorescent assays
(ELIFAs), both of which have sensitivities around 95%
but specificities in the 46% to 53% range. One point
that must be stressed when using D-dimer assays to
evaluate for thromboembolic diseases is that these
tests cannot be considered in isolation. They must
be combined with the clinical pretest probability for
a pulmonary embolism or DVT. A patient with a low
clinical pretest probability can be effectively ruled out
with a negative D-dimer study; however, a patient
with a high clinical pretest probability may not be
ruled out with a negative D-dimer and must have
additional diagnostic studies.29
A meta-analysis that included more than 47,000
patients found that the use of age-adjusted D-dimer
assays was as sensitive as conventional thresholds
in making management decisions for suspected
AUGUST 2023 • www.ebmedicine.net
pulmonary embolism patients.30
Because the normal value for a D-dimer varies
with age, an age-adjusted D-dimer should be used
in applying the assay results to any particular patient.
When using D-dimers as part of any risk stratification
tool, the treating clinician must be aware of the spe-
cific D-dimer assay used by their laboratory. D-dimer
is reported in 2 different units: FEU (fibrinogen equiv-
alent units) or DDU (D-dimer units). Although specific
formulas are used to define age-adjusted D-dimer
results, a practical formula for calculating the FEU is
to set the threshold for a positive test in individuals
aged >50 years to the patient’s age multiplied by 10.
For example, a 65-year-old patient being tested in a
laboratory with a baseline D-dimer assay threshold
of 500 ng/mL would have a threshold of 650 ng/
mL.29 Because the DDU threshold is half that of FEU,
the age correction is 5 times the patient’s age, not
10 times. In the above example, if the laboratory is
reporting in DDUs, the normal value would be 250
ng/mL and the corrected normal for a patient aged
65 years would be 325 ng/mL.
Serum Troponin and Natriuretic Peptides
Cardiac troponin T and I isoforms (cTnT and cTnI)
are expressed in cardiac muscle tissue and are not
specific for acute myocardial infarctions, but also may
occur with other medical conditions.31 Elevations
in serum troponin levels can be seen in up to 50%
of hypotensive pulmonary embolism patients, but
in very few asymptomatic patients. As a diagnostic
test, serum troponin has a sensitivity of 51% and a
specificity of 81%.32 Serum troponin determinations
are much more valuable as prognostic tests for
severity of illness or mortality than as a tool in
diagnosing pulmonary emboli.
Elevations in serum B-type natriuretic peptide
(BNP) or N-terminal-pro BNP levels can also occur in
patients with pulmonary emboli. These findings result
from stretching of the right ventricle secondary to
elevated right ventricular pressures and are more use-
ful for prognostic scoring than for diagnostic testing.
Patients with elevated pro-BNP have a 10% risk for
early death and a 23% risk for an adverse outcome.33
Imaging Studies
Chest Radiograph
A chest radiograph is useful in identifying alternative
pathology to account for a patient’s presentation, but
it is of little value in confirming or excluding a pulmo-
nary embolism. In a double-blind study, experienced
radiologists demonstrated, on plain chest x-ray, a
sensitivity of 33% and a specificity of 59%, for an
overall accuracy of 40% for the diagnosis of pulmo-
nary emboli on a plain chest x-ray.34 Plain chest x-rays
were 70% accurate in diagnosing pulmonary infarc-
tions through identification of a combination of dia-
phragm elevation, atelectasis, and pleural effusions,
8 ©2023 EB MEDICINE
but they were unable to diagnose pulmonary em-
boli.35,36 Chest radiograph reports describe a paucity
of vascular markings in pulmonary embolism patients
(the Westermark sign), or central pulmonary artery di-
lation, but these can be very subjective and are rarely
found.37 The Hampton hump is a peripheral, wedge-
shaped opacification adjacent to the pleural surface,
representing a pulmonary infarction distal to a pulmo-
nary embolus. This sign is also neither sensitive nor
specific.34 Congestive heart failure on a chest x-ray
is an independent risk factor for pulmonary emboli,
with an odds ratio (OR) of 2.34.38 Upper abdominal
pathology can produce chest pain symptoms that can
be consistent with pulmonary embolism. For this rea-
son, clinicians should examine the subdiaphragmatic
area of a chest x-ray for signs of free air, radio-opaque
gallstones, or intestinal dilations.
Computed Tomography
Computed tomographic pulmonary arteriography
(CTPA) is both sensitive and specific for the pres-
ence of clots in the pulmonary vascular tree.39,40 (See
Figure 1.) For the identification of clinically significant
blood clots, the sensitivity of CTPA varies between
96% and 100%, with a specificity of 89% to 98%.41
Multiple variations of CT angiography now exist for
the diagnosis of pulmonary emboli, including triple-
rule-out protocols to evaluate for aortic dissections
and coronary stenosis, dual-energy pulmonary CT
angiography, perfusion imaging, virtual monoen-

Figure 1. Computed Tomography Pulmonary Angiography Scans Showing Pulmonary

Embolisms

The pulmonary arteries are enhanced by contrast, but PEs appear as filling defects, as indicated by the yellow arrows.
Abbreviation: PE, pulmonary embolism.
Reprinted from Rosen's Emergency Medicine Concepts and Clinical Practice. 10th edition. Ron M. Walls, ed. Pulmonary embolism and deep vein
thrombosis. Christopher Kabrhel. Pages 1022-1041 Copyright 2023, with permission from Elsevier.

AUGUST 2023 • www.ebmedicine.net 9 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.

ergetic imaging, and low-tube-voltage scanning.
Despite subtle protocol differences, all of these
approaches use intravenous (IV) iodinated contrast
material timed to demonstrate blood flow through
the pulmonary circulation. More importantly for the
clinician, all of these approaches provide the same
95%-plus sensitivity for the detection of blood clots
in the lungs. The significance of the detection of
subsegmental pulmonary emboli remains controver-
sial, with such clots being identified in up to 9.4% of
cases.41 Even more concerning is that fact that up to
75% of identified subsegmental pulmonary emboli
are thought to be false positives.42
Radiation exposure from CTPA varies with the pro-
tocols used, ranging from 1.1 mSv to 10 mSv.43 The
generally accepted threshold for biological exposure
to produce genetic mutations is considered to be >50
mSv, well above that of a typical CTPA study.
CT pulmonary angiograms also provide informa-
tion for other thoracic organs, including the heart
and aorta. As such, some centers will perform what
is frequently termed a triple-rule-out, in which the
radiology technicians time their studies to identify
pathology in the coronary vessels and the aorta. If
performed correctly, there is no decrease in the sen-
sitivity of the study in identifying pulmonary emboli.44
The use of the triple-rule-out is particularly well-suited
to patients whose clinical presentation is consistent
with multiple possible etiologies.
Risks of Iodinated Contrast
Because a CTPA study uses iodinated contrast, it has
a risk for producing acute kidney injury. Variability in
the severity of illness, the degree of hydration, and
underlying renal function in ED patients undergoing
iodinated contrast studies makes resulting contrast-
induced nephropathy difficult to predict. Reports of
contrast-induced nephropathy range from 1.9% to
23% of patients following a diagnostic procedure
involving contrast.45 One recommended risk
stratification tool for contrast-induced nephropathy
is based on the patient’s estimated glomerular
filtration rate (eGFR)46:
• eGFR ≥45 mL/min/1.73m2: negligible risk
• eGFR 30-44 mL/min/1.73m2: intermediate risk
• eGFR <30 mL/min/1.73m2: higher risk
The presence of other risk factors (eg, diabetes
mellitus) will elevate any of these risks.46 If a CTPA
is the best diagnostic study in a critical patient, then
it needs to be performed and the possible renal
complications addressed as they occur.
Patients who are already on renal dialysis pres-
ent another challenge when undergoing pulmonary
angiography. Because of the lack of renal clear-
ance for the study’s contrast load, these patients will
require dialysis to eliminate the excess iodine. As a
general rule, hemodialysis patients undergoing these
AUGUST 2023 • www.ebmedicine.net
studies should have a dialysis session within 48 hours
of receiving diagnostic contrast. Patients managed
with peritoneal dialysis, regardless of format, should
undergo some form of dialysis within 24 hours, so this
is not a problem for these individuals.47 However, cli-
nicians should be familiar with the preferences of their
particular institution in how IV contrast is managed in
end-stage renal disease patients.
Point-of-Care Ultrasonography
Another study that may be readily available to the
emergency clinician is point-of-care ultrasound
(POCUS). The utility of this test is very provider-spe-
cific. The most useful POCUS finding indicative of a
pulmonary embolism is the identification of a throm-
bus in lower extremity veins. A meta-analysis found
that a pulmonary embolus can be seen in up to 6.9%
of patients with superficial venous thrombosis.48 Con-
comitant pulmonary embolisms and DVTs can occur
in between 40% and 70% of patients.49 The presence
of a DVT is an independent risk factor for a pulmo-
nary embolism, with an OR of 2.1 for a pulmonary
embolism.38 Interestingly, in patients with a unilateral
DVT, right-sided clots appeared more commonly than
left-sided clots; 26.7% versus 17.7%. A presumptive
diagnosis of pulmonary embolism can be made in a
patient with the appropriate clinical symptoms and a
lower extremity DVT on ultrasound examination.
Chest POCUS can also support the diagnosis of
a pulmonary embolism. Identification of subpleural
infarcts on a lung ultrasound scan was 60% sensitive
and 95.6% specific for the diagnosis of pulmonary
emboli, while identification of right ventricular dilation
was 32.7% sensitive and 90.6% specific.50
Sophisticated echocardiographic criteria exist
for the diagnosis of pulmonary emboli, including an
increased right-ventricle-to-left-ventricle size ratio;
abnormal septal motion; tricuspid regurgitation;
decreased tricuspid annular plane systolic excursion;
pulmonary artery midsystolic notching; speckle
tracking demonstrating decreased right ventricular
free wall strain; and the general appearance of a
dilated right ventricle and recognition of hypokinesis
or akinesis of the right ventricular free wall with
preservation of the apex (the McConnell sign).51-54
More practically, recognition of the McConnell sign is
within the skill set of ED clinicians and it can be seen
in 68% of pulmonary embolism patients.53 Abnormal
bowing of the intraventricular septum from the right
ventricle to the left (“D” sign) is another POCUS
finding that may be seen by emergency clinicians.
Although such septal motion is only 25% sensitive
for pulmonary embolism, its 95% specificity is useful
for confirming right ventricular overload.52 Using
a multiorgan protocol of examination of the heart,
lungs, and leg, POCUS had a sensitivity of 90% and a
specificity of 86% for pulmonary embolism.50
10 ©2023 EB MEDICINE
Pulmonary Perfusion Study
The other primary diagnostic study for patients at risk
for pulmonary emboli is the ventilation/perfusion (V/Q)
scan.55 Since the introduction of CT angiography, the
use of the V/Q scan to diagnose pulmonary emboli
has decreased markedly, and is now being used as
the sole study in as few as 7.1% of suspected patients,
despite having noninferior accuracy in the diagnosis
of this disease.55 A systematic review of diagnostic
accuracy and outcome studies utilizing the Quality
Assessment of Diagnostic Accuracy Studies tool found
that single-photon emission CT (SPECT) V/Q studies
demonstrated a mean sensitivity of 96% and a specific-
ity of 94%.56 The migration to CT over V/Q scanning
for the diagnosis of suspect pulmonary embolism likely
stems from the rapidity of the CT study as well as the
ability of CT to detect other lung pathology.
Pulmonary Angiography
Dedicated pulmonary angiography is a standard
angiography procedure in which a formal digital
angiogram is performed though a catheter placed
into the pulmonary artery. Although extremely
accurate, the procedure requires an interventional
radiologist or cardiologist and a dedicated
angiography facility.
Magnetic Resonance Angiography
Magnetic resonance angiography is a more recent
addition to the diagnostic studies used to identify
pulmonary emboli. Because of the time required to
acquire an image with this technique, at present, up
to 30% of tests are technically unreadable. Of those
that are interpretable, the sensitivity is only 78%
but the specificity is 99%.57 At present, magnetic
resonance angiography is not regarded as a first-
line diagnostic study for patients with suspected
pulmonary embolism.
Risk Stratification Categorization
A number of risk stratification scores based on the
physiologic characteristics of pulmonary embolism
patients have been developed.58,59 Clinical risk
classification tools are used to create a pretest
probability score to determine the need for further
diagnostic studies to rule in or rule out the presence
of a pulmonary embolism. The Clinical Pathway for
Table 3. European Society of Cardiology Prognostic Classification of Pulmonary Embolism33
Risk Hemodynamic Instability
Low risk Negative
Intermediate-low risk Negative
Intermediate-high risk Negative
High risk Sustained hypotension or bradycardia or shock or inotropic support
Abbreviations: BNP, B-type natriuretic peptide; CT, computed tomography.
AUGUST 2023 • www.ebmedicine.net
the Diagnostic Approach to Suspected Pulmonary
Embolism (page 19) summarizes how a clinical risk
classification system might be combined with diagnostic
studies to diagnose a pulmonary embolism.
In contrast, prognostic risk classifications com-
bine physiologic and diagnostic studies to determine
the severity of the pulmonary embolism in a patient.
A number of scoring systems are in current use to
describe patients for prognostic risk stratification. In
one scoring system, the term massive pulmonary em-
boli is applied to patients with abnormal vital signs,
including: systolic blood pressure <90 mm Hg for >15
minutes; a need for vasopressors; clinical shock; or
bradycardia. The term submassive pulmonary emboli
is applied to patients with an abnormal or dilated
right ventricle on echocardiogram or CT scan or ab-
normal troponin levels or natriuretic peptides (either
BNP or pro-BNP).
A scoring system developed by the European
Society of Cardiology uses sustained hypotension,
bradycardia, need for vasopressors, and clinical
shock to define the high-risk group. (See Table 3.)
Intermediate-high risk is defined as both the presence
of right ventricle abnormality and either an elevated
troponin or natriuretic peptide. Intermediate-low risk
is defined by only an abnormal right ventricle or an
abnormal laboratory study, troponin, or BNP. Other
scoring systems include the simplified Pulmonary Em-
bolism Index (sPESI) (Table 4, page 12) and the Bova
Score for Pulmonary Embolism Complications (Table
5, page 12). The advantage of these scoring systems
is that they can be used not only to predict morbidity
and mortality but also direct treatments.
Online calculators for these scores are
available at www.MDCalc.com
• Simplified PESI (Pulmonary Embolism
Severity Index): https://www.mdcalc.
com/calc/1247/simplified-pesi-pulmonary-
embolism-severity-index
• Bova Score for Pulmonary Embolism Compli-
cations: https://www.mdcalc.com/calc/4004/
bova-score-pulmonary-embolism-complica-
tions
Right Ventricular Dysfunction on CT or Elevated Biomarkers
Echocardiogram Troponin, BNP, or Pro-BNP
Negative Negative
CT positive or echocardiogram positive Negative
CT positive and echocardiogram positive Negative
11 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.
n Treatment
Treatment is dictated by the clinical stability of the
patient. Unconscious patients, those with altered
mental status, or those with profound lethargy may
require stabilization of their airway with endotracheal
intubation before initiation of any diagnostics.
For more stable patients, supportive care begins
with assurance of patient oxygenation. In animal
models of acute pulmonary embolism, oxygen ther-
apy reduced right ventricle afterload and decreased
right ventricle mechanical work.60 Maintaining a pulse
oximetry level >95% should be the treatment goal.
For minimally symptomatic patients, delivery of sup-
plemental oxygen can be via nasal cannula or simple
face mask. If the oxygen deficit requires >6 L/min of
nasal oxygen to maintain an adequate pulse oximetry
level, then a more advanced delivery system should
be considered. Noninvasive respiratory support can
be provided by either high-flow nasal cannula (HFNC)
or noninvasive positive-pressure ventilation (NIPPV).
HFNC systems are simple to initiate, well toler-
ated, and provide fraction of inspired oxygen (FiO2)
levels up to 100%. HFNC systems function through
the use of elevated gas flows to wash out the upper
airway dead spaces of exhaled high CO2 and low O2
gases and replace them with low CO2 high O2 gas.60
Successful use of HFNC systems for pulmonary em-
bolism patients has been described only in some case
reports and observational studies.61-63
NIPPV systems are either continuous positive air-
way pressure systems (CPAP) or bilevel positive airway
pressure systems (BiPAP). In both of these systems,
positive pressure is maintained through all phases of
the respiratory cycle. One disadvantage of NIPPV sys-
tems is that this positive pressure is also transmitted
to the intrathoracic cavity, decreasing venous return
to the heart. This is advantageous in cases of pulmo-
nary overload, such as in congestive heart failure, but
may be detrimental in pulmonary embolus patients.64
Endotracheal intubation provides 100% oxygen-
ation but has the same limitations as NIPPV. Be-
cause there is no native breath to generate negative
intrathoracic pressure, ventilation by endotracheal
intubation results in only passive blood flow into the
right side of the heart. In addition, positive-pressure
ventilation increases right ventricular afterload, plac-
ing further stress on a distended right ventricle. If
endotracheal intubation is necessary, the minimum
amount of positive end-expiratory pressure should be
used, along with lung protective ventilator settings.
Induction agents for rapid sequence intubation
should take into account the fragile cardiovascular
status of these patients. Medications that produce
hypotension (eg, propofol, remifentanil, barbiturates)
should be avoided, while drugs such as ketamine and
etomidate may be preferred. Providing additional
intravascular fluid to augment this blood flow may
help create greater right ventricular preload but has
additional detrimental effects in a distended right
ventricle.65 In cases of severe hypoxia, endotracheal
intubation may be the best option despite its
detrimental effects on right ventricular function.
Fluid Management
Patients with stable vital signs will generally have
no additional fluid requirements as long as they are
permitted ad lib access to liquids. For those who are
hypotensive, some degree of fluid therapy may be re-
quired. Intuitively, it would seem that increasing right
ventricular preload would augment blood flow to the
lungs to help bypass the obstructing clots.65 However,
physiologically, the exact opposite seems to occur.
The added fluid further dilates the right ventricle and
leads to right ventricular failure. As the right ventricle
fails, less blood is pumped across the pulmonary
vascular bed and less blood is presented to the left
ventricle. This produces a functional hypovolemic
state, which then leads to systemic hypotension.66,67
Further cardiovascular compromise can result as the
distended right ventricle displaces the intraventricular
septum into the left ventricle, disrupting systemic
cardiac output.
The right ventricle evolved to contract against
a low pressure afterload, and it struggles when it

Table 4. Simplified Pulmonary Embolism Table 5. Bova Score for Pulmonary

Index (sPESI) Embolism Complications
Variable Points Variable Points
Age >80 years 1 Systolic blood pressure 90-100 mm Hg 2
History of cancer 1 Elevated cardiac troponin 2
History of chronic cardiopulmonary disease 1 Right ventricular dysfunction on computed 2
Pulse ≥110 beats/min 1 tomography or echocardiogram

Systolic blood pressure <100 mm Hg 1 Heart rate ≥110 beats/min 1

Arterial blood saturation <90% 1 Total Points ______

Total Points ______ Stage I, low risk 0-2 points

Low risk 0 Stage II, intermediate risk 3-4 points

High risk ≥1 Stage III, high risk >4 points

AUGUST 2023 • www.ebmedicine.net 12 ©2023 EB MEDICINE

encounters the sudden onset of pulmonary hy-
pertension. Though counterintuitive, decreasing
intravascular volume could improve right ventricular
function. In an observational study, normotensive
patients receiving furosemide demonstrated improve-
ments in shock index 0.82 versus 0.63 and simplified
pulmonary embolism severity (sPESI) index ≥1: 45%
versus 55%.68 In a study of intermediate-risk pulmo-
nary embolism patients, 80 mg of furosemide re-
duced sPESI characteristics in 51.5% of diuretic-treat-
ed patients compared to 37.1% of placebo patients.69
Improvements in peak tricuspid annular systolic
velocity and heart rate were observed in the diuretic
group of a third study comparing furosemide and
fluid expansion in pulmonary embolism patients.70
Vasoactive Agents
As with ventricular dysfunction involving the left
ventricle, the use of vasopressors can be considered
for patients with right ventricular failure. Agents
such as norepinephrine or dobutamine can be used
to maintain systemic blood pressure in patients in
shock.33 Any vasoactive agent will be limited by
filling pressures in the left ventricle. A medication
such as milrinone with both inotropy and vascular
relaxant effects may be more effective but needs to
be added cautiously in hypotensive patients. There
is evidence that milrinone will produce pulmonary
artery dilation, which can then augment blood
flow and decrease right ventricular afterload.33 All
vasodilators are nonspecific and although they may
dilate the pulmonary circulation, they may also dilate
the systemic circulation, leading to hypotension.66,67
Specific pulmonary artery vasodilators (eg, inhaled
nitric oxide) have shown mixed results in the ability
to improve right ventricular function in pulmonary
embolism patients. Newer experimental agents such
as terlipressin have shown promise in animal models,
but definitive human studies are pending.71,72
Table 6. Initial Anticoagulant Therapy for Pulmonary Embolism
Medication Route Initial Dose
Apixaban (DOAC) Oral 10 mg twice daily × 1 wk
Rivaroxaban (DOAC) Oral 15 mg twice daily × 3 wk
Edoxaban (DOAC) Oral Weight-based dosing:
>60 kg: 60 mg once daily
≤60 kg: 30 mg once daily with
parenteral bridge for at least 5 days
Unfractionated heparin IV 80 units/kg bolus followed by 18 units/hr
Enoxaparin (LMWH) SubQ 1 mg/kg twice daily or 1.5 mg/kg/day
Warfarin Oral 2.5-5 mg with parenteral bridge
Abbreviations: aPTT, activated partial thromboplastin time; DOAC, direct oral anticoagulant; INR, international normalized ratio; IV, intravenous; LMWH,
low-molecular-weight heparin; subQ, subcutaneously.
AUGUST 2023 • www.ebmedicine.net 13
Anticoagulation
Anticoagulation is the mainstay of pulmonary embo-
lism management to prevent further clot propaga-
tion and to facilitate dissolution of any existing clot.
Table 6 summarizes initial anticoagulation options for
pulmonary embolus patients. In the ED, the choice
of anticoagulant is guided by the individual patient’s
clinical scenario. For pulmonary embolism, there are
currently 3 direct oral anticoagulant (DOAC) fac-
tor Xa inhibitors commonly used in clinical practice:
apixaban, rivaroxaban, and edoxaban. Major ad-
vantages of these agents are that they can be orally
loaded at the time of the patient’s initial encounter,
and they generally produce anticoagulation within a
few hours of administration. These DOACs have pre-
dictable therapeutic profiles, with no need for blood
sample monitoring. These characteristics make them
appropriate for patients with stable vital signs and
normal oxygen saturation levels.73-75
More clinically compromised patients will require
initial parenteral therapy. Infusions of unfractionated
heparin have relatively predictable pharmacokinetics,
although it does require periodic measurements of
the activated partial thromboplastin time (aPTT). A
major advantage of heparin is its ability to be phar-
macologically reversed with protamine should the
patient require a surgical procedure.75 Low-molecular-
weight heparins (LMWHs), given subcutaneously,
have a rapid onset and achieve therapeutic levels
within hours, making them potentially more beneficial
for the initial treatment of symptomatic pulmonary
emboli for patients without renal impairment.33,75
Warfarin was the oral anticoagulant traditionally
used for outpatient management of pulmonary em-
boli. Although effective, it has an erratic therapeutic
profile and requires periodic blood samplings to mea-
sure the patient’s international normalized ratio (INR).
Patients on warfarin will require a bridge of heparin or
LMWH until a therapeutic INR level is achieved.75
Maintenance Dose Comments
5 mg twice daily Requires renal adjustment
20 mg once daily Requires renal adjustment
Weight-based dosing: Requires renal adjustment
>60 kg: 60 mg once daily
≤60 kg: 30 mg once daily
Titrated every 6 hr based on aPTT No renal adjustment
1 mg/kg twice daily or 1.5 mg/kg/day Requires renal adjustment
Dose adjustments based on INR, Several factors affect therapeutic
with INR goal of 2-3 efficacy
www.ebmedicine.net
© 2023 EB MEDICINE. ALL RIGHTS RESERVED.
Thrombolytics
Although anticoagulants help prevent additional
clot propagation, active dissolution is obtained
only through the use of thrombolytics, which
include alteplase, urokinase, and streptokinase.
Alteplase (tissue plasminogen activator, tPA) is the
primary means of lysing clots. These agents must
be administered systemically or through pulmonary
artery catheters. Systemic thrombolytics are reserved
for use in unstable patients. Compared to heparin,
systemic thrombolytics show a reduction in overall
mortality, particularly among high-risk patients (OR,
0.59), and a lower need for treatment escalation
(OR, 0.34) but at the cost of increased major adverse
hemorrhage (OR, 2.91).76
Alteplase is effective for decreasing CT-docu-
mented right ventricular abnormalities;76 however,
there is no consensus on dosing of alteplase in this
scenario. Some dosing strategies that have been
described in the literature and have been used in
patients with differing degrees of symptom severity
include the following:
• 0.6 mg/kg IV bolus followed by the remainder of
100 mg over 2 hours
• 50-100 mg IV over 2 hours
• 50-100 mg IV push
• 50 mg IV push followed by 50 mg IV over 2 hours
Tenecteplase is a modified tPA that is also used
in patients with pulmonary embolism. It has the
advantage of delivery as a single bolus injection and
does not require follow-up infusion. Nonetheless, the
evidence in support of tenecteplase over alteplase is
currently lacking.77
Because of the risk for major hemorrhage as-
sociated with the use of any systemic thrombolytic,
care must be taken to avoid administering them
to patients who have contraindications to these
agents. Table 7 lists the contraindications to systemic
thrombolysis of pulmonary emboli.
Catheter-Directed Thrombolysis
In addition to systemic administration of thrombo-
lytics, these medications can be delivered directly to
the clot via catheter-directed thrombolysis via a pul-
monary artery catheter. In these catheters, ports for
thrombolytic delivery are coupled with an ultrasonic
agitator to help disperse the medication into and
around the clot. This invasive approach will require
the services of an interventional clinician as well as
a fluoroscopic suite.79 This approach is generally ap-
plied to patients who are at intermediate-high risk,
high risk with cardiovascular instability, or who have
contraindications for systemic thrombolysis. In a study
of intermediate-risk patients, the placement of the
catheter-directed thrombolysis catheter took only 15
minutes and resulted in a reduction of the pulmonary
artery obstruction by 35.9%.80
AUGUST 2023 • www.ebmedicine.net
Thrombectomy
As with emboli in other areas of the body, mechani-
cal removal of a clot in the pulmonary circulation is
a therapeutic option. Various retrieval devices have
been developed to mechanically remove clots in the
pulmonary circulation. Some mechanically disrupt
the clot; others suction it back into a catheter; while
other use pressure jets to break the clot into small
fragments. All of these devices require the services
of an intravascular interventional physician to direct
the thrombectomy device into the pulmonary circula-
tion. Technical success rates in removing clots from
the pulmonary circulation range as high as 97.1%,
with clinical success rates of 90.7%.81 The impact on
clinical outcome of clot removal is less well defined,
however, and the clinical indications for these proce-
dures are controversial.82
Operative Thoracotomy
Extraction of clots through a formal thoracotomy
remains an option for patients refractory to any other
therapy. This approach is the most invasive and is re-
served for extremely large clot loads in patients in ex-
tremis or those failing other less-invasive approaches.
This is also the preferred approach for patients with
a clot in transit, generally a clot straddling a patent
foramen ovale. Mortality among patients undergoing
this procedure is understandably high, ranging from
11% to 75%, with the highest death rates occurring in
patients suffering preprocedure cardiac arrest.83
Table 7. Contraindications to Systemic
Thrombolytic Treatment of Pulmonary
Embolism78
Absolute Contraindications
• Prior intracranial hemorrhage
• Structural intracranial cerebrovascular disease
• Malignant intracranial neoplasm
• Ischemic stroke within prior 3 months
• Suspected aortic dissection
• Active bleeding or bleeding diathesis
• Recent surgery near spinal canal or brain
• Recent significant closed-head or facial trauma with bony fracture or
brain injury
Relative Contraindications
• Age >75 years
• Current use of anticoagulants
• Pregnancy
• Noncompressible vascular punctures
• Traumatic or prolonged cardiopulmonary resuscitation
• Internal bleeding in past 2-4 weeks
• History of chronic, severe, poorly controlled hypertension
• Dementia
• Ischemic stroke >3 months prior
• Major surgery within prior 3 weeks
14 ©2023 EB MEDICINE
Extracorporeal Membrane Oxygenation
Extracorporeal membrane oxygenation (ECMO) is
a final option for patients unable to be adequately
stabilized through other means. ECMO may be
delivered as either a venous-to-venous (VV) route
or a venous-to-arterial (VA) route. In VV ECMO, the
procedure assumes the gas exchange responsibility
of the lungs, providing oxygenation while removing
carbon dioxide. In these patients, the left ventricle
still provides the systemic cardiac output. In VA
ECMO, the procedure also assumes the responsibility
for providing the systemic circulation. ECMO is most
commonly used as a bridge to a more definitive
therapeutic procedure to remove the offending clot,
though high-quality data are lacking.83,84
Patient Management
Patient management for an acute pulmonary
embolism must be individualized. Clinical decisions
can be extremely complex and often require the
input of multiple consultants. The development of
institution-specific pulmonary embolism response
teams (PERTs) has helped to facilitate real-time
decisions for these patients. The PERT composition
can vary, but frequently will include members from
emergency medicine, pulmonology, interventional
radiology, interventional cardiology, and critical
care, plus others, depending on the institution. PERT
notification criteria vary, but, in general, become
active for patients determined to be at intermediate-
high risk and high risk.79,85
The specific management approach to the patient
with a pulmonary embolism is controversial, at best.
Multiple organizations have developed treatment
algorithms based on clinical risk assessments for
the treatment of pulmonary emboli. Stable patients
with no hypoxia, tachycardia, or dyspnea who
meet low-risk criteria can be safely managed with
anticoagulation only. These patients may also be
candidates for outpatient care.
All intermediate-risk and high-risk patients will
require hospitalization, preferably with continuous
cardiac monitoring. Supplemental oxygen in the form
of nasal cannula may be required to maintain an oxy-
gen saturation >95%. The specific therapy to address
the pulmonary embolism remains controversial. These
patients may be managed with initial anticoagulation
with a LMWH or heparin.45
With the introduction of catheter-directed
procedures for thrombolysis and thrombectomy, the
treatment of patients who are intermediate-high risk
and high risk is changing. However, to date, there
are no definitive data to identify which patients
can benefit from these interventions.81,86-88 The
Clinical Pathway for Risk-Directed Management
of Pulmonary Embolism (page 20) presents a risk-
assessment therapeutic approach to the management
of pulmonary embolism patients.
AUGUST 2023 • www.ebmedicine.net
n Special Populations
Pulmonary Embolism in Pregnant Patients
Pregnancy is an independent risk factor for the
development of pulmonary emboli, including the
prepartum and postpartum periods, and is a leading
cause of maternal mortality, causing 1.13 deaths per
100,000 maternities.89 Pregnant patients also present
a diagnostic challenge in that many of the signs and
symptoms of pulmonary emboli are present as normal
characteristics of pregnancy. The YEARS criteria for
clinical pretest probability categorization is the only
algorithm with dedicated pregnancy evaluation.89
Pulmonary embolism diagnosis is further compli-
cated by the risks to the mother and fetus with the
use of diagnostic CTPA or pulmonary perfusion stud-
ies;90,91 however, both studies present a radiation risk
that is well below the 50 mSv threshold for biologic
injury. CTPA may present an exposure of 3 to 10 mSV
to the mother’s breast tissue and a 0.05 to 0.5 mSV
dose to the fetus, while a V/Q scan will present a fetal
exposure of 0.2 to 0.6 mSV.92
Magnetic resonance testing may be considered
for pregnant patients, particularly if the iron supple-
ment ferumoxytol is used for contrast. At present
though, this has limited usefulness in most clinical
sites.93 The use of D-dimer values is also limited as
a screening test because the thresholds for positive
values vary through the trimesters of the pregnancy.
In one report in which 500 ng/mL was considered the
normal threshold in nonpregnant patients, D-dimer
intervals were determined to be 110 to 400 ng/mL
in the first trimester; 140 to 750 ng/mL in the sec-
ond trimester, and 160 to 1300 ng/mL in the third.94
The Clinical Pathway for Emergency Department
Management of Pulmonary Embolism in Pregnant
Patients (page 21) presents an approach to suspect-
ed pulmonary embolism in pregnancy.90
Treatment of pulmonary embolism in pregnancy
in low-risk patients is with LMWHs.95 However, once
a patient’s risk rises to the intermediate-risk or high-
risk category, more difficult management decisions
must be made. The use of thrombolytics (regardless
of delivery method), catheter interventions, ECMO,
and surgical embolectomy all come into play in these
patients and are best decided upon with a PERT team
or with input from multiple consultants. None of these
options is clearly superior to any others or present
superior risk-benefit ratios.33
Pulmonary Embolism and COVID-19 Patients
Infection with the SARS-CoV-2 virus, COVID-19
disease, can lead to elevated pulmonary thrombo-
embolic risks. Two mechanisms have been proposed
for this increase. The first is a hypercoagulable state,
leading to large-vessel thrombi. The second is a
direct endovascular injury secondary to viral infection
of endothelial cells. Pulmonary embolism rates vary
depending on the reporting source,96-98 but one
15 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.
systematic review places the incidence at 17.5% for
emergency department patients, 23.9% for general
wards, and 48.6% for intensive care unit patients.98
Diagnosis of pulmonary embolism in patients
either with or following infection with the SARS-CoV-2
virus is hampered due to the overlapping symptoms
of the 2 diseases, undermining the accuracy of clinical
decision rules. D-dimer analysis encounters the same
problem, although raising the threshold to 1000 ng/mL
may improve the specificity of the test, as COVID-19
patients with pulmonary emboli, in general, have a
higher D-dimer level than non-COVID patients.97
Unfortunately, there is no good clinical practice ad-
justment to help distinguish patients with pulmonary
emboli and no infection from patients with shortness of
breath and hypoxia secondary to their viral infection.
Once diagnosed, the management of SARS-
COV-2 patients with pulmonary emboli is essentially
the same as for noninfected individuals.98,99
n Controversies and Cutting Edge
5 Recommendations
Catheter-directed thrombolysis
To Apply and mechanical
in Practice
thrombectomy have introduced new treatment
options for the management of higher-risk pulmo-
nary embolism 5patients. At present though, there is
Recommendations
To Apply in Practice
5 Things That Will Change
5 Recommendations
Your Practice
To Apply in Practice
1. Recognize high-risk factors for pulmonary
emboli, and consider pulmonary embolism
as a cause of a patient’s symptoms when pre-
senting to the emergency department.
2. Consider outpatient management. Applica-
tion of tools such as the Hestia criteria allow
clinicians to identify patients at low risk for
complications who may safely be discharged
from the ED.
3. Use clinical classifications to guide inpatient
management. Application of clinical risk
scores can help direct the clinician toward the
most appropriate treatment. This will limit the
overuse of invasive procedures that do not
impact patient outcomes.
4. Interpret D-dimer studies appropriately.
Understanding the concept of age-adjusted
D-dimer studies will prevent diagnosis based
on false-positive results.
5. Use pretest probability risk stratification tools
to limit diagnostic studies. The use of algo-
rithms to create risk categories for patients
with potential pulmonary emboli can direct
emergency clinicians on the most effective
use of radiographic studies.
AUGUST 2023 • www.ebmedicine.net
limited, if any, evidence to identify which patients
may benefit from these new therapies. Intermediate-
high and high-risk individuals appear to be the group
most likely to require some form of more aggressive
therapy including catheter-directed thrombolysis,
mechanical thrombectomy, and even ECMO or surgi-
cal thrombectomy. Unfortunately, the role of more
aggressive treatment beyond systemic thrombolysis
remains undefined. The mortality rate for conserva-
tively managed patients in the intermediate-high–risk
group or those with an sPESI score of 0 can be as
low as 1% to 3%, making objective proof of outcome
improvements for these procedures difficult to obtain.
Multiple studies have used normalization of the right-
ventricle-to-left ventricle ratio to ≤0.9 as a surrogate
marker in single-arm studies on invasive management
techniques. However, at this time there is no random-
ized study comparing aggressive and conservative
treatments in the management of intermediate-high-
risk patients. Comparisons of systemic thrombolytics
with mechanical thrombectomy have shown advan-
tages and disadvantages to both approaches but no
clear-cut optimal management approach. The input
of a PERT team can be extremely valuable in sorting
through the options in the care of these patients.
n Disposition
Despite the potential severity of pulmonary emboli
and the risk for significant morbidity and mortality,
the disposition of these patients ranges from inten-
sive care unit admission to outpatient home care.
Low-risk patients meeting the Hestia criteria (See Ta-
ble 8) may be candidates for outpatient management
of their pulmonary emboli. Anticoagulation must be
initiated for these patients in the emergency depart-
ment and may include either a DOAC or a LMWH.
Patients managed with warfarin are best admitted to
the hospital for bridging therapy until anticoagulation
is achieved. Low-risk patients not meeting the Hestia
criteria should be admitted to the hospital, preferably
in a unit with cardiovascular monitoring capabilities.
Table 8. Hestia Criteria for Outpatient
Treatment of Pulmonary Embolism3
All Criteria Must be Answered “No” to Qualify for Outpatient
Pulmonary Embolism Therapy:
• Hemodynamic instability
• Thrombolysis or embolectomy required
• Active bleeding or high risk for bleed
• Oxygen required to maintain pulse oxygen >90%
• Pulmonary embolism diagnosed during anticoagulant treatment
• Recent intravenous pain medication
• Other medical or social issue requiring hospitalization
• Creatine clearance <30 mL/min* (Cockcroft-Gault formula)
• Severe liver disease
• Pregnancy
• History of heparin-induced thrombocytopenia
16 ©2023 EB MEDICINE
 Case Conclusions
For the obese 55-year-old man with 2 days of exertional dyspnea…
Because all previous studies did not explain his dyspnea and mild tachycardia, you obtained a D-dimer,
which returned at 1250 ng/mL. You obtained a chest CT angiogram that revealed the presence of a large
CASE 1

pulmonary embolism. You began anticoagulation with LMWH. A Doppler study also revealed a DVT in
his left leg, and an echocardiogram depicted right ventricular strain. His troponin I returned normal. You
contacted your PERT team. This patient was intermediate-high risk, which now opened the debate for the
best management. Ultimately, because of the patient’s size, it was determined that a catheter embolectomy
was the best course. The procedure was performed, the patient did well, and was discharged to home.

For the 65-year-old woman with dyspnea…

CASE 2

The patient required anticoagulation, but the question arose as to which agent to use and the ideal
disposition. She met low-risk criteria by sPESI and she met the Hestia criteria for outpatient management.
You discussed the case with the PERT team, and with shared decision-making with the patient, she was
started on a DOAC and scheduled to follow up with the pulmonologist from the PERT team in 2 days.

For the 60-year-old woman who arrived via EMS cyanotic, tachypneic, and tachycardic…
This patient was clearly a high-risk pulmonary embolism patient, even without any diagnostic studies. A
right humeral intraosseous access was obtained. She became lethargic, with a progressively dropping
respiratory rate. She underwent rapid sequence intubation with ketamine and rocuronium, and her
oxygenation improved to a pulse oximetry of 85% on 100% bag-valve mask ventilation, with an end-tidal
CASE 3

carbon dioxide level of 60 mm Hg. A right internal jugular catheter was placed and she was administered
alteplase 50 mg IV over 2 hours. A portable chest x-ray was negative. Bedside echocardiography
demonstrated a dilated right ventricle. The patient’s oxygen saturation gradually improved to 95%, and CO2
level decreased to 40 mm Hg. She was transferred to the CT scanner, where a pulmonary saddle embolism
was identified. Her blood pressure stabilized at 100/70 mm Hg, and her heart rate decreased to 110 beats/
min. Her oxygen continued to improve over the next 3 hours and she was transferred to the intensive
care unit. Following a rocky 1 month hospitalization, the patient was discharged home with a return to
premorbid baseline health status.

High-risk patients, by definition, have unstable n Time- and Cost-Effective Strategies

vital signs and should be cared for in a critical care-
level unit that can provide close monitoring of all vital
signs. Intermediate-risk patients (whether intermedi-
ate-low or intermediate-high) will also require cardio-
vascular monitoring but may be cared for in another
monitored unit in the hospital, depending on the
logistics of that particular facility. A hospital-specific
PERT consult may be useful in directing the admission
location for admitted patients.
n Summary
Acute pulmonary embolism patients present a unique
challenge to emergency clinicians. Fortunately, the
creation of risk stratification criteria help with both the
diagnostic workup of potential pulmonary embolism
patients as well as their therapeutic management.
Having an understanding of how and when to apply
these criteria allows emergency clinicians to deliver
well-supported, evidence-based care across the entire
spectrum of acute pulmonary embolism patients.
• Invasive management techniques for pulmo-
nary emboli are impressive, particularly when a
thrombectomy is performed and multiple large
collections of clots are removed. However, there
is no evidence that such procedures change pa-
tient outcomes, especially when it comes to mor-
tality. Considering the costs and risks of catheter
thrombectomies, more research will be required
before these procedures become the norm for
intermediate-risk patients.
• The use of clinical risk diagnosis scores such as
PERC, Wells, and YEARS can limit the excessive
use of high-cost tests such as CTPAs and V/Q
scans.
• Use the Hestia criteria to discharge low-risk
patients, as it is very cost effective and safe.
• Use the YEARS criteria in pregnant patients at risk
for pulmonary embolism to eliminate unnecessary
radiation studies.
• Use the age-adjusted D-dimer criteria to reduce
the number of elderly patients requiring further
studies for pulmonary embolism.

AUGUST 2023 • www.ebmedicine.net 17 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.

 Risk Management Pitfalls for Pulmonary Embolism
in the Emergency Department
1. “The patient had normal vital signs, they could
not have a pulmonary embolism.” Abnormal vi-
tal signs are of value in alerting a clinician to look
for a pulmonary embolism, but the reverse is not
true. Patients with pulmonary emboli can have
normal vital signs.
2. “She had no pleuritic chest pain, so a pulmo-
nary embolism should not be on the differen-
tial.” Pleuritic chest pain occurs in less than 50%
of patients, while nonpleuritic chest pain can
occur in 17% of cases.
3. “The onset of shortness of breath was over
days. That is not how a pulmonary embolism
presents.” It is true that approximately 67% of
patients with a pulmonary embolism will describe
their dyspnea as “sudden” in onset, occurring
within minutes, but this still leaves a gradual
onset occurring in about one-third of cases.
4. “It doesn't matter what the patient’s blood
pressure showed, or her normal troponin and
BNP. There was a large clot on the CTPA and
a dilated right ventricle. She needed tPA.” In
patients who are stable, low-risk, or intermediate-
low risk, the value of tPA is not well established.
There is real risk for bleeding with tPA, as well. At
present, tPA should be used only in high-risk pa-
tients and should be considered in intermediate-
high risk patients.
5. “I am an emergency physician. I can manage
my patients without a PERT team.” It may not
be the standard of care to consult a PERT team
for every pulmonary embolism patient; however,
getting expert consultants involved in the care
of a patient, especially one who is not low-risk, is
always a good idea.
AUGUST 2023 • www.ebmedicine.net
6. “The patient met most of the Hestia criteria
for outpatient management, isn’t that good
enough?” For outpatient management of
pulmonary embolus patients, it is prudent to be
certain that discharged patients meet all of the
Hestia criteria or some other outpatient scoring
system. This diagnosis has the potential to take
a downward turn very quickly, so it is best to
be conservative regarding which patients are
admitted and which are sent home.
7. “I started the patient on warfarin, so he was
anticoagulated.” Warfarin is a vitamin K antago-
nist, and it takes time to become effective. If it is
to be used for pulmonary embolism patients, a
bridge with a rapid-acting anticoagulant must be
used until the warfarin becomes therapeutic.
8. “The patient’s rGeneva score was 4. That is
almost low-risk.” Low-risk is ≤3. You can state in
your note that the patient was intermediate-risk
but you decided that the entire clinical picture
did not warrant further workup, but do not state
the patient was “almost” low-risk.
9. “The patient’s chest pain was clearly cardiac,
and I ruled them out with a negative troponin
test and an ECG.” The pain from a pulmonary
embolism can mimic that from an acute myocar-
dial infarction. Just because you have ruled out
one does not mean you do not need to consider
the other.
10. “I didn’t think the recent surgery was an is-
sue. The patient needed tPA.” If the patient is
high risk and has an absolute contraindication to
tPA, then the clinician should attempt to arrange
another approach, which might include catheter-
directed tPA or a thrombectomy.
18 ©2023 EB MEDICINE
 Clinical Pathway for the Diagnostic Approach
to Pulmonary Embolism Management

Patient presents with suspected pulmonary embolism

Apply clinical probability assessment

(determined by prediction rule) (Class I)

Low or intermediate probability High probability

Perform D-dimer test (Class I) Perform CTPA or V/Q scan (Class I)

Positive? Positive?

NO YES YES NO

Perform CTPA or V/Q

No treatment scan (Class I) YES Treat Pursue other diagnoses
Positive?

Abbreviations: CTPA, computed tomographic pulmonary arteriography; V/Q, ventilation/perfusion.

Class of Evidence Definitions

Each action in the clinical pathways section of Emergency Medicine Practice receives a score based on the following definitions.
Class I Class II
• Always acceptable, safe • Safe, acceptable Class III Indeterminate
• Definitely useful • Probably useful • May be acceptable • Continuing area of research
• Proven in both efficacy and effectiveness • Possibly useful • No recommendations until further
Level of Evidence: • Considered optional or alternative research
Level of Evidence: • Generally higher levels of evidence treatments
• One or more large prospective studies • Nonrandomized or retrospective stud- Level of Evidence:
are present (with rare exceptions) ies: historic, cohort, or case control Level of Evidence: • Evidence not available
• High-quality meta-analyses studies • Generally lower or intermediate levels • Higher studies in progress
• Study results consistently positive and • Less robust randomized controlled trials of evidence • Results inconsistent, contradictory
compelling • Results consistently positive • Case series, animal studies, • Results not compelling
consensus panels
• Occasionally positive results

This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a patient’s individual
needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright © 2023 EB Medicine. www.ebmedicine.net. No part of this publication may be reproduced in any format without written consent of EB Medicine.

AUGUST 2023 • www.ebmedicine.net 19 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.

 Clinical Pathway for Risk-Directed Management
of Pulmonary Embolism

Patient has confirmed pulmonary embolism

Initiate anticoagulation (see Table 6) (Class I)

Risk-stratify patient (Class I)

Low risk Intermediate-low risk Intermediate-high risk High risk

Continue anticoagulation Are there

NO Is there clinical deterioration to high risk? YES
(Class I) contraindications to
thrombolysis?
(see Table 7)

YES YES NO

Consider reduced-dose thrombolysis or mechanical thrombectomy

YES, relative
(Class III)

Consider mechanical thrombectomy (Class III) YES, absolute

Systemic thrombolysis,
full or reduced dose
(Class III)

For Class of Evidence definitions, see page 19.

AUGUST 2023 • www.ebmedicine.net 20 ©2023 EB MEDICINE

 Clinical Pathway for Emergency Department Management
of Pulmonary Embolism in Pregnant Patients

Pregnant patient presents with

suspicion for pulmonary embolism

• Perform D-dimer study (Class I)

• Assess YEARS criteria* (Class II)

YES Clinical signs of deep vein thrombosis? NO

Perform compression ultrasound of Any YEARS criteria positive?

lower extremities (Class I) (Class III)

YES NO

D-dimer <1000
Positive for deep vein thrombosis? NO D-dimer <500 ng/mL?
ng/mL?

YES YES YES NO

No pulmonary Perform CTPA; if

Initiate anticoagulation (see Table 6)
embolism positive, initiate
anticoagulation

*YEARS criteria:
• Clinical signs of deep vein thrombosis
• Hemoptysis
• Pulmonary embolism is the most likely diagnosis

MDCalc online tool for YEARS:

https://www.mdcalc.com/calc/4067/years-algorithm-for-pulmonary-embolism-pe

Abbreviation: CTPA, computed tomography pulmonary angiography.

For Class of Evidence definitions, see page 19.

AUGUST 2023 • www.ebmedicine.net 21 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.

n References
Evidence-based medicine requires a critical appraisal
of the literature based upon study methodology and
number of subjects. Not all references are equally
robust. The findings of a large, prospective, random­
ized, and blinded trial should carry more weight than
a case report.
To help the reader judge the strength of each
reference, pertinent information about the study will
be included in bold type following the ref­erence,
where available. In addition, the most informative
references cited in this paper, as determined by
the authors, are noted by an asterisk (*) next to the
number of the reference.
1. Khan F, Tritschler T, Kahn SR, et al. Venous thromboembolism.
Lancet. 2021;398(10294):64-77. (Review)
2. Kahn SR, de Wit K. Pulmonary embolism. N Engl J Med.
2022;387(1):45-57. (Review)
3.* Westafer LM, Long B, Gottlieb M. Managing pulmonary embo-
lism. Ann of Emerg Med. 2023:1-9. (Review)
DOI: 10.1016/j.annemergmed.2023.01.019
4. Mansella G, Keil C, Nickel CH, et al. Delayed diagnosis in
pulmonary embolism: frequency, patient characteristics, and
outcome. Respiration. 2020;99(7):589-597. (Retrospective case
comparison; 1119 patients)
5. Stone J, Hangge P, Albadawi H, et al. Deep vein thrombosis:
pathogenesis, diagnosis, and medical management. Cardiovasc
Diagn Ther. 2017;7(Suppl 3):S276-S284. (Review)
6. Rali PM, Criner GJ. Submassive pulmonary embolism. Am J
Respir Crit Care Med. 2018;198(5):588-598. (Review)
7. Kaptein FHJ, Kroft LJM, Hammerschlag G, et al. Pulmo-
nary infarction in acute pulmonary embolism. Thromb Res.
2021;202:162-169. (Review)
8. Wenger N, Sebastian T, Engelberger RP, et al. Pulmonary em-
bolism and deep vein thrombosis: similar but different. Thromb
Res. 2021;206:88-98. (Review)
9. Wang H, Huang Y, Xu CW, et al. Clinical analysis of tumor and
non-tumor patients complicated with pulmonary embolism. Int
J Clin Exp Med. 2015;8(10):18729-18736.
10. Senst B, Tadi P, Basit H, et al. Hypercoagulability. StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022.
(Review)
11. Gimbel IA, Mulder FI, Bosch FTM, et al. Pulmonary em-
bolism at autopsy in cancer patients. J Thromb Haemost.
2021;19(5):1228-1235. (Retrospective cohort study; 9571
patients)
12. Au C, Gupta E, Khaing P, et al. Clinical presentations and out-
comes in pulmonary embolism patients with cancer. J Thromb
Thrombolysis. 2021;51(2):430-436. (Retrospective case series;
581 patients)
13.* Stein PD, Beemath A, Matta F, et al. Clinical characteristics of
patients with acute pulmonary embolism: data from PIOPED
II. Am J Med. 2007;120(10):871-879. (Analysis of prospective
data base; 824 patients)
DOI: 10.1016/j.amjmed.2007.03.024
14. Kline JA, Kabrhel C. Emergency evaluation for pulmonary em-
bolism, part 1: clinical factors that increase risk. J Emerg Med.
2015;48(6):771-780. (Review)
15.* Badertscher P, du Fay de Lavallaz J, Hammerer-Lercher A, et al.
Prevalence of pulmonary embolism in patients with syncope.
J Am Coll Cardiol. 2019;74(6):744-754. (Prospective observa-
tional study; 1380 patients) DOI: 10.1016/j.jacc.2019.06.020
AUGUST 2023 • www.ebmedicine.net
16. Richmond C, Jolly H, Isles C. Syncope in pulmonary em-
bolism: a retrospective cohort study. Postgrad Med J.
2021;97(1154):789-791. (Retrospective cohort study; 224
patients)
17. Kline JA, Hernandez-Nino J, Jones AE, et al. Prospective study
of the clinical features and outcomes of emergency department
patients with delayed diagnosis of pulmonary embolism. Acad
Emerg Med. 2007;14(7):592-598. (Prospective observational
study; 161 patients)
18.* Kline JA, Corredor DM, Hogg MM, et al. Normalization of vital
signs does not reduce the probability of acute pulmonary em-
bolism in symptomatic emergency department patients. Acad
Emerg Med. 2012;19(1):11-17. (Prospective observational
study; 192 patients)
DOI: 10.1111/j.1553-2712.2011.01253.x
19. Becattini C, Vedovati MC, Pruszczyk P, et al. Oxygen satu-
ration or respiratory rate to improve risk stratification in
hemodynamically stable patients with acute pulmonary embo-
lism. J Thromb Haemost. 2018;16(12):2397-2402. (Prospective
cohort study; 946 patients)
20. Bowers T, Goldstein JA. Hemodynamic compromise in pulmo-
nary embolism: “a tale of two ventricles”. Catheter Cardiovasc
Interv. 2021;97(2):299-300. (Pathophysiology presentation)
21. Chan TF, Ngian VJJ, Hsu K, et al. Pulmonary embolism: clinical
presentation and diagnosis in the oldest old. Intern Med J.
2020;50(5):627-631. (Retrospective cohort study; 302 pa-
tients)
22. Adeyinka A, Kondamudi NP. Cyanosis. StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2022. (Review)
23. Busse LW, Vourlekis JS. Submassive pulmonary embolism. Crit
Care Clin. 2014;30(3):447-473. (Review)
24. Vyas V, Goyal A. Acute pulmonary embolism. StatPearls [Inter-
net]. Treasure Island (FL): StatPearls Publishing; 2022. (Review)
25. Kline JA, Garrett JS, Sarmiento EJ, et al. Over-testing for
suspected pulmonary embolism in American emergency
departments: the continuing epidemic. Circ Cardiovasc Qual
Outcomes. 2020;13(1):E005753. (Database analysis)
26. Rodger MA, Maser E, Stiell I, et al. The interobserver reliability
of pretest probability assessment in patients with suspected
pulmonary embolism. Thromb Res. 2005;116(2):101-107. (Pro-
spective cohort; 110 patients)
27. Thomson D, Kourounis G, Trenear R, et al. ECG in suspected
pulmonary embolism. Postgrad Med J. 2019;95(1119):12-17.
(Retrospective case control; 1397 patients)
28. Friberg L, Svennberg E. A diagnosis of atrial fibrillation is not a
predictor for pulmonary embolism. Thromb Res. 2020;195:238-
242. (Retrospective registry study; 1.5 million patients)
29. Freund Y, Chauvin A, Jimenez S, et al. Effect of a diagnostic
strategy using an elevated and age-adjusted D-dimer threshold
on thromboembolic events in emergency department patients
with suspected pulmonary embolism: a randomized clinical
trial. JAMA. 2021;326(21):2141-2149. (Prospective random-
ized trial; 726 patients)
30.* Iwuji K, Almekdash H, Nugent KM, et al. Age-adjusted D-dimer
in the prediction of pulmonary embolism: systematic review
and meta-analysis. J Prim Care Community Health. 2021;12:1-
8. (Systematic review) DOI: 10.1177/21501327211054996
31. Chauin A. The main causes and mechanisms of increase in
cardiac troponin concentrations other than acute myocardial
infarction (part 1): physical exertion, inflammatory heart disease,
pulmonary embolism, renal failure, sepsis. Vasc Health Risk
Manag. 2021;17:601-617. (Review)
32. Kilinc G, Dogan OT, Berk S, et al. Significance of serum car-
diac troponin I levels in pulmonary embolism. J Thorac Dis.
2012;4(6):588-593. (Prospective observational study; 106
patients)
22 ©2023 EB MEDICINE
33.* Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC
guidelines for the diagnosis and management of acute pulmo-
nary embolism developed in collaboration with the European
Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603.
(Guidelines) DOI: 10.1093/eurheartj/ehz405
34. Greenspan RH, Ravin CE, Polansky SM, et al. Accuracy of the
chest radiograph in diagnosis of pulmonary embolism. Invest
Radiol. 1982;17(6):539-543. (Prospective case series; 152
patients)
35. Talbot S, Worthington BS, Roebuck EJ. Radiographic signs
of pulmonary embolism and pulmonary infarction. Thorax.
1973;28(2):198-203. (Autopsy study; 123 patients)
36. Coche E, Verschuren F, Hainaut P, et al. Pulmonary embolism
findings on chest radiographs and multislice spiral CT. Eur
Radiol. 2004;14(7):1241-1248. (Matched control series)
37. Buckner CB, Walker CW, Purnell GL. Pulmonary embo-
lism: chest radiographic abnormalities. J Thorac Imaging.
1989;4(4):23-27. (Descriptive review)
38. Hou J, Wang W, Cai H, et al. Patients with right lower extrem-
ity deep vein thrombosis have a higher risk of symptomatic
pulmonary embolism: a retrospective study of 1585 patients.
Ann Vasc Surg. 2022;81:240-248. (Retrospective study; 1585
patients)
39. Knollmann F, Chu L, Lang JA. CT angiography for the detection
of pulmonary embolism: role of tube voltage and contrast injec-
tion rate on diagnostic confidence. Acad Radiol. 2022;29:S91-
S97. (Retrospective comparison; 401 patients)
40. Leithner D, Gruber-Rouh T, Beeres M, et al. 90-kVp low-
tube-voltage CT pulmonary angiography in combination
with advanced modeled iterative reconstruction algorithm:
effects on radiation dose, image quality and diagnostic ac-
curacy for the detection of pulmonary embolism. Br J Radiol.
2018;91(1088):1-6. (Retrospective case series; 40 patients)
41. Wiener RS, Schwartz LM, Woloshin S. When a test is too good:
how CT pulmonary angiograms find pulmonary emboli that do
not need to be found. BMJ. 2013;347:F3368. (Opinion)
42. Keeling D, Klok FA, Le Gal G. Controversies in venous throm-
boembolism--2015. Blood Rev. 2016;30(1):27-33. (Review)
43. Takahashi EA, Yoon HC. Four-year cumulative radiation
exposure in patients undergoing computed tomography
angiography for suspected pulmonary embolism. Radiol Res
Pract. 2013;2013:482403. (Retrospective case series; 300
patients)
44. Russo V, Sportoletti C, Scalas G, et al. The triple rule out CT
in acute chest pain: a challenge for emergency radiologists?
Emerg Radiol. 2021;28(4):735-742. (Prospective observational
study; 350 patients)
45. Ong MY, Koh JJ, Kothan S, et al. The incidence and associated
risk factors of contrast-induced nephropathy after contrast-
enhanced computed tomography in the emergency setting:
a systematic review. Life (Basel). 2022;12(6):826. (Systematic
review)
46. Rudnick MR, Leonberg-Yoo AK, Litt HI, et al. The controversy of
contrast-induced nephropathy with intravenous contrast: what
is the risk? Am J Kidney Dis. 2020;75(1):105-113. (Review)
47. Younathan CM, Kaude JV, Cook MD, et al. Dialysis is not
indicated immediately after administration of nonionic contrast
agents in patients with end-stage renal disease treated by
maintenance dialysis. AJR Am J Roentgenol. 1994;163(4):969-
971. (Review)
48. Di Minno MN, Ambrosino P, Ambrosini F, et al. Prevalence
of deep vein thrombosis and pulmonary embolism in pa-
tients with superficial vein thrombosis: a systematic review
and meta-analysis. J Thromb Haemost. 2016;14(5):964-972.
(Meta-analysis; 9326 patients)
49. Shirkhodaie C, Lattell J, Paul J, et al. Concomitant lower-
AUGUST 2023 • www.ebmedicine.net
extremity deep vein thrombosis in patients with pulmonary
embolism undergoing catheter-directed therapy. J Invasive
Cardiol. 2021;33(11):e910-e915. (Retrospective case series;
137 patients)
50. Nazerian P, Vanni S, Volpicelli G, et al. Accuracy of point-of-care
multiorgan ultrasonography for the diagnosis of pulmonary em-
bolism. Chest. 2014;145(5):950-957. (Prospective case series;
357 patients)
51. Alerhand S, Sundaram T, Gottlieb M. What are the
echocardiographic findings of acute right ventricular strain that
suggest pulmonary embolism? Anaesth Crit Care Pain Med.
2021;40(2):100852. (Descriptive review article)
52. Alerhand S, Hickey SM. Tricuspid Annular Plane Systolic Excur-
sion (TAPSE) for risk stratification and prognostication of pa-
tients with pulmonary embolism. J Emerg Med. 2020;58(3):449-
456. (Review)
53. Mediratta A, Addetia K, Medvedofsky D, et al.
Echocardiographic diagnosis of acute pulmonary embo-
lism in patients with McConnell’s sign. Echocardiography.
2016;33(5):696-702. (Retrospective case series; 167 patients)
54. Daley JI, Dwyer KH, Grunwald Z, et al. Increased sensitivity of
focused cardiac ultrasound for pulmonary embolism in emer-
gency department patients with abnormal vital signs. Acad
Emerg Med. 2019;26(11):1211-1220. (Prospective case series;
1432 patients)
55. Bonnefoy PB, Prevot N, Mehdipoor G, et al. Ventilation/
perfusion (V/Q) scanning in contemporary patients with
pulmonary embolism: utilization rates and predictors of use in
a multinational study. J Thromb Thrombolysis. 2022;53(4):829-
840. (Database analysis; 26,540 patients)
56. Le Roux PY, Robin P, Tromeur C, et al. Ventilation/perfusion
SPECT for the diagnosis of pulmonary embolism: a systematic
review. J Thromb Haemost. 2020;18(11):2910-2920.
(Systematic review)
57. Benson DG, Schiebler ML, Repplinger MD, et al. Contrast-en-
hanced pulmonary MRA for the primary diagnosis of pulmonary
embolism: current state of the art and future directions. Br J
Radiol. 2017;90(1074):20160901. (Review)
58. Maraziti G, Cimini LA, Becattini C. Risk stratification to optimize
the management of acute pulmonary embolism. Expert Rev
Cardiovasc Ther. 2022;20(5):377-387. (Review)
59. Triantafyllou GA, O’Corragain O, Rivera-Lebron B, et al. Risk
stratification in acute pulmonary embolism: the latest algo-
rithms. Semin Respir Crit Care Med. 2021;42(2):183-198.
(Review)
60. Lyhne MD, Hansen JV, Dragsbæk SJ, et al. Oxygen therapy
lowers right ventricular afterload in experimental acute pulmo-
nary embolism. Crit Care Med. 2021;49(9):e891-e901. (Animal
model)
61. Sharma S, Danckers M, Sanghavi D, et al. High flow nasal
cannula. StatPearls [Internet]. Treasure Island (FL): StatPearls
Publishing; 2022. (Review)
62. Messika J, Goutorbe P, Hajage D, et al. Severe pulmonary em-
bolism managed with high-flow nasal cannula oxygen therapy.
Eur J Emerg Med. 2017;24(3):230-232. (Case report)
63. Aksakal A, Saglam L, Kerget B, et al. Comparison of the ef-
fectiveness of high-flow and conventional nasal cannula oxygen
therapy in pulmonary embolism patients with acute hypoxemic
respiratory failure. Tuberk Toraks. 2021;69(4):469-476. (Prospec-
tive randomized controlled trial; 58 patients)
64. Johnson KG. APAP, BPAP, CPAP, and new modes of positive air-
way pressure therapy. Adv Exp Med Biol. 2022;1384:297-330.
(Review)
65. Pinsky MR. The right ventricle: interaction with the pulmonary
circulation. Crit Care. 2016;20(1):266. (Review)
66. Crager SE, Humphreys C. Right ventricular failure and pulmo-
23 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.
 nary hypertension. Emerg Med Clin North Am. 2022;40(3):519-
537. (Review)
67. Cassady SJ, Ramani GV. Right heart failure in pulmonary hyper-
tension. Cardiol Clin. 2020;38(2):243-255. (Review)
68. Lim P, Delmas C, Sanchez O, et al. Diuretic vs. placebo in
intermediate-risk acute pulmonary embolism: a randomized
clinical trial. Eur Heart J Acute Cardiovasc Care. 2022;11(1):2-9.
(Prospective randomized controlled trial; 276 patients)
69. Ternacle J, Gallet R, Mekontso-Dessap A, et al. Diuretics in
normotensive patients with acute pulmonary embolism and
right ventricular dilatation. Circ J. 2013;77(10):2612-2618. (Ret-
rospective case series; 70 patients)
70. Schouver ED, Chiche O, Bouvier P, et al. Diuretics versus vol-
ume expansion in acute submassive pulmonary embolism. Arch
Cardiovasc Dis. 2017;110(11):616-625. (Prospective random-
ized controlled trial; 46 patients)
71. Schultz J, Andersen A, Lyhne MD, et al. Terlipressin increases
systemic and lowers pulmonary arterial pressure in experimen-
tal acute pulmonary embolism. Crit Care Med. 2020;48(4):e308-
e315. (Animal study)
72. Kline JA, Puskarich MA, Jones AE, et al. Inhaled nitric oxide
to treat intermediate risk pulmonary embolism: a multicenter
randomized controlled trial. Nitric Oxide. 2019;84:60-68. (Ran-
domized controlled trial; 38 patients)
73. Palmirotta R. Direct oral anticoagulants (DOAC): are we ready
for a pharmacogenetic approach? J Pers Med. 2021;12(1):17.
(Review)
74. Wells PS, Kovacs MJ, Bormanis J, et al. Expanding eligibility for
outpatient treatment of deep venous thrombosis and pulmo-
nary embolism with low-molecular-weight heparin: a compari-
son of patient self-injection with homecare injection. Arch Intern
Med. 1998;158(16):1809-1812. (Prospective observational
study; 194 patients)
75. Leentjens J, Peters M, Esselink AC, et al. Initial anticoagulation
in patients with pulmonary embolism: thrombolysis,
unfractionated heparin, LMWH, fondaparinux, or DOACs? Br J
Clin Pharmacol. 2017;83(11):2356-2366. (Review)
76. Marti C, John G, Konstantinides S, et al. Systemic thrombolytic
therapy for acute pulmonary embolism: a systematic review and
meta-analysis. Eur Heart J. 2015;36(10):605-614. (Review)
77. Igneri LA, Hammer JM. Systemic thrombolytic therapy for
massive and submassive pulmonary embolism. J Pharm Pract.
2020;33(1):74-89. (Review)
78. Jaff MR, McMurtry MS, Archer SL, et al. Management of mas-
sive and submassive pulmonary embolism, iliofemoral deep
vein thrombosis, and chronic thromboembolic pulmonary
hypertension: a scientific statement from the American Heart
Association. Circulation. 2011;123(16):1788-1830. (Scientific
statement)
79. Brown K, Devarapally S, Lee L, et al. Catheter directed
thrombolysis of pulmonary embolism. StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2022. (Review)
80. Bashir R, Foster M, Iskander A, et al. Pharmacomechanical
catheter-directed thrombolysis with the bashir endovascular
catheter for acute pulmonary embolism: the RESCUE study.
JACC Cardiovasc Interv. 2022;15(23):2427-2436. (Prospective
observational study; 109 patients)
81. Chandra VM, Khaja MS, Kryger MC, et al. Mechanical aspira-
tion thrombectomy for the treatment of pulmonary embolism: a
systematic review and meta-analysis. Vasc Med. 2022;27(6):574-
584. (Review)
82.* Desai KR. Mechanical thrombectomy in pulmonary embolism:
ready for prime time? JACC Cardiovasc Interv. 2021;14(3):330-
332. (Opinion) DOI: 10.1016/j.jcin.2020.11.002
83. de Perrot M. Role of extracorporeal membrane oxygenation
and surgical embolectomy in acute pulmonary embolism. Curr
AUGUST 2023 • www.ebmedicine.net
Opin Pulm Med. 2022;28(5):384-390. (Opinion)
84. Goldhaber SZ. ECMO and surgical embolectomy: two potent
tools to manage high-risk pulmonary embolism. J Am Coll
Cardiol. 2020;76(8):912-915. (Opinion)
85.* Rivera-Lebron BN, Rali PM, Tapson VF. The PERT concept: a
step-by-step approach to managing pulmonary embolism.
Chest. 2021;159(1):347-355. (Review)
DOI: 10.1016/j.chest.2020.07.065
86. Jolly M, Phillips J. Pulmonary embolism: current role of catheter
treatment options and operative thrombectomy. Surg Clin
North Am. 2018;98(2):279-292. (Review)
87. Al-Khadra Y, Missula V, Al-Bast B, et al. Outcomes of mechani-
cal thrombectomy compared with systemic thrombolysis in
pulmonary embolism: a comprehensive evaluation from the
National Inpatient Sample Database. J Endovasc Ther. 2022.
(Database review; 16,890 patients)
88. Rivera-Lebron B, McDaniel M, Ahrar K, et al. Diagnosis, treat-
ment and follow up of acute pulmonary embolism: consensus
practice from the PERT consortium. Clin Appl Thromb Hemost.
2019;25:1-16. (Review)
89. Hobohm L, Farmakis IT, Munzel T, et al. Pulmonary embo-
lism and pregnancy-challenges in diagnostic and therapeu-
tic decisions in high-risk patients. Front Cardiovasc Med.
2022;9:856594. (Review)
90. van der Pol LM, Tromeur C, Bistervels IM, et al. Pregnancy-
adapted YEARS algorithm for diagnosis of suspected pul-
monary embolism. N Engl J Med. 2019;380(12):1139-1149.
(Prospective observational study; 510 patients)
91. Righini M, Robert-Ebadi H, Elias A, et al. Diagnosis of pul-
monary embolism during pregnancy: a multicenter pro-
spective management outcome study. Ann Intern Med.
2018;169(11):766-773. (Prospective observational study; 441
patients)
92. Bates SM. Pulmonary embolism in pregnancy. Semin Respir Crit
Care Med. 2021;42(2):284-298. (Review)
93. Starekova J, Nagle SK, Schiebler ML, et al. Pulmonary MRA
during pregnancy: early experience with ferumoxytol. J Magn
Reson Imaging. 2022. (Observational review; 98 patients)
94. Ercan S, Ozkan S, Yucel N, et al. Establishing reference intervals
for D-dimer to trimesters. J Matern Fetal Neonatal Med.
2015;28(8):983-987. (Retrospective review; 1448 patients)
95. Wiegers HMG, Middeldorp S. Contemporary best practice in
the management of pulmonary embolism during pregnancy.
Ther Adv Respir Dis. 2020;14:1-20. (Review)
96. Poor HD. Pulmonary thrombosis and thromboembolism in
COVID-19. Chest. 2021;160(4):1471-1480. (Review)
97. Kwee RM, Adams HJA, Kwee TC. Pulmonary embolism in
patients with COVID-19 and value of D-dimer assessment: a
meta-analysis. Eur Radiol. 2021;31(11):8168-8186. (Meta analy-
sis)
98. Cui LY, Cheng WW, Mou ZW, et al. Risk factors for pulmonary
embolism in patients with COVID-19: a systemic review and
meta-analysis. Int J Infect Dis. 2021;111:154-163. (Meta analy-
sis)
99. Adams E, Broce M, Mousa A. Proposed algorithm for treatment
of pulmonary embolism in COVID-19 patients. Ann Vasc Surg.
2021;70:282-285. (Opinion)
24 ©2023 EB MEDICINE
n CME Questions
Current subscribers receive CME credit
absolutely free by completing the
following test. Each issue includes 4 AMA
PRA Category 1 CreditsTM, 4 ACEP
Category I credits, 4 AAFP Prescribed
credits, and 4 AOA Category 2-B credits.
Online testing is available for current and archived
issues. To receive your free CME credits for this
issue, scan the QR code below with your
smartphone or visit www.ebmedicine.net/0823
1. Which is included in the Virchow triad as a
cause of venous thrombus formation?
a. Thrombocytopenia
b. Hypoxia
c. Hyperventilation
d. Venous stasis
2. What is the most common genetic factor
leading to a hypercoagulable state?
a. Factor V Leiden
b. Thalassemia major
c. Trisomy 21
d. Congenital adrenal hyperplasia
3. In the PIOPED II study, what was the most
common risk factor found for pulmonary
embolism?
a. Recent trauma
b. Body mass index <25
c. Hypertension
d. Female sex
4. In what percentage of patients with pulmonary
embolism are abnormalities found in the
cardiac examination?
a. 1%
b. 10%
c. 22%
d. 78%
5. Visual cyanosis requires what degree of
hemoglobin desaturation?
a. 1 g/dL
b. 3-5 g/dL
c. 10 g/dL
d. There is no specific value
AUGUST 2023 • www.ebmedicine.net
6. If the normal threshold for a D-dimer test
is 500 ng/mL, then the accepted D-dimer
threshold for a 75-year-old woman would be:
a. 75 ng/mL
b. 500 ng/mL
c. 750 ng/mL
d. 1000 ng/mL
7. The Hampton hump on a chest x-ray of
a person with a pulmonary embolism is
described as:
a. A peripheral wedge-shaped opacification
b. An elevation of the right hemidiaphragm
c. A right-sided mediastinal bulge
d. An irregularly shaped aortic silhouette
8. When comparing computed tomography
pulmonary angiography (CTPA) and
ventilation/perfusion (V/Q) studies for the
diagnosis of pulmonary embolism, which of the
following is an accurate statement?
a. V/Q scans are more sensitive than CTPA
b. CTPA has a sensitivity approximately 10%
greater than V/Q scanning
c. Both exhibit an approximate 95% sensitivity
d. Neither test is >85% sensitive
9. A person with a pulmonary embolism, no
hemodynamic instability, right ventricular
dilation, and normal troponin and natriuretic
peptide levels would be classified by the
European Cardiology Society as:
a. Low risk
b. Intermediate-low risk
c. Intermediate-high risk
d. High risk
10. A pregnant patient in her third trimester has a
YEARS score of 0 and a D-dimer >1000 ng/mL.
What would be the next step in her care?
a. CTPA
b. Immediate administration of tissue
plasminogen activator
c. Compression ultrasonography
d. Discharge to home
25 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.
 Stay up-to-date on the most relevant
topics in emergency medicine with EMplify
at www.ebmedicine.net/podcast
The Emergency Medicine Practice Editorial Board
EDITOR-IN-CHIEF
Andy Jagoda, MD, FACEP
Professor and Chair Emeritus,
Department of Emergency
Medicine; Director, Center for
Emergency Medicine Education
and Research, Icahn School of
Medicine at Mount Sinai, New
York, NY
ASSOCIATE EDITOR-IN-CHIEF
Kaushal Shah, MD, FACEP
Assistant Dean of Academic
Advising, Vice Chair of
Education, Professor of
Clinical Emergency Medicine,
Department of Emergency
Medicine, Weill Cornell School of
Medicine, New York, NY
EDITORIAL BOARD
Saadia Akhtar, MD, FACEP
Associate Professor, Department
of Emergency Medicine,
Associate Dean for Graduate
Medical Education, Program
Director, Emergency Medicine
Residency, Mount Sinai Beth
Israel, New York, NY
William J. Brady, MD, FACEP,
FAAEM
Professor of Emergency Medicine
and Medicine; Medical Director,
Emergency Management,
UVA Medical Center; Medical
Director, Albemarle County Fire
Rescue, Charlottesville, VA
Calvin A. Brown III, MD
Director of Physician
Compliance, Credentialing
and Urgent Care Services,
Department of Emergency
Medicine, Brigham and Women's
Hospital, Boston, MA
Peter DeBlieux, MD
Professor of Clinical Medicine,
Louisiana State University School
of Medicine; Chief Experience
Officer, University Medical
Center, New Orleans, LA
Deborah Diercks, MD, MS,
FACEP, FACC
Professor and Chair, Department
of Emergency Medicine,
University of Texas Southwestern
Medical Center, Dallas, TX
AUGUST 2023 • www.ebmedicine.net
Daniel J. Egan, MD
Harvard Affiliated Emergency
Medicine Residency,
Massachusetts General Hospital/
Brigham and Women's Hospital,
Boston, MA
Marie-Carmelle Elie, MD
Professor and Chair, Department
of Emergency Medicine
University of Alabama at
Birmingham, Birmingham, AL
Nicholas Genes, MD, PhD
Clinical Assistant Professor,
Ronald O. Perelman Department
of Emergency Medicine, NYU
Grossman School of Medicine,
New York, NY
Michael A. Gibbs, MD, FACEP
Professor and Chair, Department
of Emergency Medicine,
Carolinas Medical Center,
University of North Carolina
School of Medicine,
Chapel Hill, NC
Steven A. Godwin, MD, FACEP
Professor and Chair, Department
of Emergency Medicine,
Assistant Dean, Simulation
Education, University of
Florida COM-Jacksonville,
Jacksonville, FL
Joseph Habboushe, MD MBA
Assistant Professor of Clinical
Emergency Medicine,
Department of Emergency
Medicine, Weill Cornell School
of Medicine, New York, NY; Co-
founder and CEO, MDCalc
Eric Legome, MD
Chair, Emergency Medicine,
Mount Sinai West & Mount Sinai
St. Luke's; Vice Chair, Academic
Affairs for Emergency Medicine,
Mount Sinai Health System, Icahn
School of Medicine at Mount
Sinai, New York, NY
Keith A. Marill, MD, MS
Associate Professor, Department
of Emergency Medicine, Harvard
Medical School, Massachusetts
General Hospital, Boston, MA
Angela M. Mills, MD, FACEP
Professor and Chair, Department
of Emergency Medicine,
Columbia University Vagelos
College of Physicians &
Surgeons, New York, NY
27
Charles V. Pollack Jr., MA, MD,
FACEP, FAAEM, FAHA, FACC,
FESC
Clinician-Scientist, Department
of Emergency Medicine,
University of Mississippi School
of Medicine, Jackson MS
Ali S. Raja, MD, MBA, MPH
Executive Vice Chair, Emergency
Medicine, Massachusetts General
Hospital; Professor of Emergency
Medicine and Radiology, Harvard
Medical School, Boston, MA
Robert L. Rogers, MD, FACEP,
FAAEM, FACP
Assistant Professor of Emergency
Medicine, The University of
Maryland School of Medicine,
Baltimore, MD
Alfred Sacchetti, MD, FACEP
Assistant Clinical Professor,
Department of Emergency
Medicine, Thomas Jefferson
University, Philadelphia, PA
Robert Schiller, MD
Chair, Department of Family
Medicine, Beth Israel Medical
Center; Senior Faculty, Family
Medicine and Community
Health, Icahn School of Medicine
at Mount Sinai, New York, NY
Scott Silvers, MD, FACEP
Associate Professor of
Emergency Medicine, Chair of
Facilities and Planning, Mayo
Clinic, Jacksonville, FL
Corey M. Slovis, MD, FACP,
FACEP
Professor and Chair Emeritus,
Department of Emergency
Medicine, Vanderbilt University
Medical Center, Nashville, TN
Stephen H. Thomas, MD, MPH
Department of Emergency
Medicine, Beth Israel Deaconess
Medical Center and Harvard
Medical School, Boston, MA
Ron M. Walls, MD
Professor and COO, Department
of Emergency Medicine, Brigham
and Women's Hospital, Harvard
Medical School, Boston, MA
© 2023 EB MEDICINE. ALL RIGHTS RESERVED.
CRITICAL CARE EDITORS
William A. Knight IV, MD,
FACEP, FNCS
Associate Professor of
Emergency Medicine and
Neurosurgery, Medical Director,
EM Advanced Practice Provider
Program; Associate Medical
Director, Neuroscience ICU,
University of Cincinnati,
Cincinnati, OH
Scott D. Weingart, MD, FCCM
Editor-in-Chief, emCrit.org
PHARMACOLOGY EDITOR
Aimee Mishler, PharmD, BCPS
Emergency Medicine Pharmacist,
St. Luke's Health System,
Boise, ID
RESEARCH EDITOR
Joseph D. Toscano, MD
Chief, Department of Emergency
Medicine, San Ramon Regional
Medical Center, San Ramon, CA
INTERNATIONAL EDITORS
Peter Cameron, MD
Academic Director, The Alfred
Emergency and Trauma Centre,
Monash University, Melbourne,
Australia
Andrea Duca, MD
Attending Emergency Physician,
Ospedale Papa Giovanni XXIII,
Bergamo, Italy
Suzanne Y.G. Peeters, MD
Attending Emergency Physician,
Flevo Teaching Hospital, Almere,
The Netherlands
Edgardo Menendez, MD,
FIFEM
Professor in Medicine and
Emergency Medicine; Director of
EM, Churruca Hospital of Buenos
Aires University, Buenos Aires,
Argentina
Dhanadol Rojanasarntikul, MD
Attending Physician, Emergency
Medicine, King Chulalongkorn
Memorial Hospital; Faculty
of Medicine, Chulalongkorn
University, Thailand
Edin Zelihic, MD
Head, Department of Emergency
Medicine, Leopoldina Hospital,
Schweinfurt, Germany
 Points & Pearls
QUICK READ
AUGUST 2023 | VOLUME 25 | ISSUE 8
Points
• Even with appropriate care, approximately 15%-
30% of patients with pulmonary embolism (PE)
will die within 90 days,1-3 potentially from the un-
derlying medical pathology that led to the clot.
• Chest pain, dyspnea, and hemoptysis are com-
mon signs of PE; establishing the time of onset of
symptoms can help determine the cause.
• Isolated syncope with no other symptoms sug-
gestive for PE is not an indication for an evalua-
tion for thromboembolic disease.
• Other findings in PE include tachypnea, tachycar-
dia, cyanosis, lower extremity edema, and deep
vein thrombosis.
• Scoring systems for determining clinical pretest
probability include the Wells, rGeneva, PERC,
and YEARS criteria. (See Table 2.)
• Electrocardiogram is useful, though not diagnos-
tic, with 25% of patients having normal tracings.27
• Age-adjusted D-dimer should be used.
• D-dimer levels change with duration of the clot.29
• Serum troponin levels32 and elevations in serum
natriuretic peptide levels are more valuable as
prognostic for severity of illness and mortality
than in diagnosis of PE.
• Chest radiographs have little value in confirming
or excluding PE; however, they may be helpful in
identifying alternative pathology.35-38
• The estimated glomerular filtration rate (eGFR)
can be used as a risk stratification tool to predict
contrast-induced nephropathy following comput-
ed tomographic pulmonary arteriography (CTPA).
• Concomitant lower extremity DVTs and PEs can
occur in 40%-70% of patients.49
• A multiorgan point-of-care ultrasound protocol of
examination of the heart, lungs, and leg has 90%
sensitivity and 86% specificity for PE.50
• Prognostic risk classifications use physiologic and
diagnostic criteria to determine severity of PE.
Tables 3, 4, and 5 present 3 classification systems.
• Fluid management and vasoactive agents may be
appropriate in some circumstances.
• Systemic thrombolytics are reserved for use in un-
stable patients. See Table 7 for contraindications.
• Thrombolytics can be delivered via pulmo-
nary artery catheter, but this use requires an
AUGUST 2023 • www.ebmedicine.net
Evidence-Based Management
of Pulmonary Embolism in
the Emergency Department
Pearls
• The most common risk factors for PE are fe-
male sex, immobilization, recent surgery, ma-
lignancy, and travel >4 hours in the previous
month. Table 1 lists other clinical risk factors.
• Primary pulmonary pathologies such as COPD,
asthma, pneumonia, pneumothorax, and
pleuritis should be on the differential for sus-
pected PE.
• Vital signs in PE may be normal; hypotension is
the least specific vital sign (5%).20
• Clinical gestalt alone demonstrates poor
performance in excluding the need for further
testing.25,26
• D-dimer assays should be used in combination
with a patient‘s clinical pretest probability to
determine whether PE can be ruled out or ad-
ditional diagnostic studies are needed.29
• CTPA is sensitive and specific for the presence
of clots in the pulmonary vascular tree.39,40
Figure 1 shows PEs on CTPA.
• Maintaining pulse oximetry >95 is the treat-
ment goal, delivered via nasal cannula, high-
flow nasal cannula, or noninvasive positive-
pressure ventilation.
• Anticoagulation is the mainstay of treatment to
prevent further clot propagation. See Table 6
for recommendations for initial anticoagulant
therapy.
interventionalist clinician to administer.
• Thrombectomy, operative thoracotomy, and
extracorporeal membrane oxygenation (ECMO)
may be options for some patients, as available.
• The pulmonary embolism response team (PERT) is
a multidisciplinary team of clinicians that assists in
coordination of care in institutions where available.
• PE in pregnant patients is a significant cause of
maternal mortality. Though low-molecular weight
heparin can be given to low-risk patients, higher
risk patients require input from a PERT team or
multiple consultants.
• Patients meeting Hestia criteria (see Table 8) may
be candidates for outpatient management.
28 ©2023 EB MEDICINE