December 2019 | Volume 3 Issue 12
Editor-in-Chief: Mel Herbert, MD
Managing Editor: Jessica Mason, MD
Executive Editor: Stuart Swadron, MD
www.emrap.org
PULMONARY EMBOLISM
Jessica Mason MD, Mel Herbert MD, Stuart Swadron MD
Peer Reviewer: Anand Swaminathan, MD
Print Editor: Whitney Johnson MD/MS
* Drugs and doses are a guide only, always check a second source and follow local practice guidelines
Take Home Points:
The diagnosis of pulmonary embolism (PE) is approached by first establishing a pre-test probability
For experienced clinicians, this can be by clinical gestalt
A decision tool such as the Wells or Geneva score can be used
Low risk patients can be ruled out (more specifically risk of PE <2%) using the PERC rule or with a negative D-dimer
The PERC rule can eliminate the need for further testing
Adjusted D-dimer cutoffs can be used in patients > 50
Age x 10 for Fibrinogen Equivalent Units (FEUs)
Age x 5 for D Dimer Units (DDUs)
Moderate risk patients are more controversial
Some protocols utilize D-dimer and others proceed directly to imaging
High risk patients should proceed to directly to imaging
Imaging options include CT pulmonary angiography (used in most protocols), ventilation-perfusion scanning
and bilateral lower extremity ultrasound
Empiric anticoagulation prior to the results of definitive testing, is appropriate in high risk patients without
contraindications
Initial treatment is with unfractionated heparin, low molecular weight heparin or a direct oral anticoagulant
Thrombolytics (e.g., alteplase) are reserved for patients in shock (e.g., hypotensive)
Pregnant patients suspected of having PE are best managed in accordance with local policies and resources.
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Background
Venous thromboembolism (VTE), abnormal clotting in the veins, can occur throughout the body. We most commonly think of
deep venous thrombosis (DVT) in the legs, but it can also occur in the upper extremities, pelvis, and even the dural venous
sinuses of the brain. Moreover, DVT and PE exist on a huge spectrum from mild or even clinically silent to life threatening,
leading to severe hypoxia and hemodynamic collapse.
Pulmonary thromboembolism or pulmonary embolism (PE) occurs when a clot (embolus) travels centrally in the venous
circulation through the right side of the heart to embolize in the pulmonary arteries. Thus, deep venous thrombosis (DVT)
and PE describe different stages along the same pathologic process. In fact, PE is found in as many as 40% of all patients
diagnosed with DVT. Inversely, in patients with a PE, about 70% are found to have a DVT.
In this episode of C3, we will focus on patients with PE. After a discussion of the key features to look for on history, examination and ECG, we will cover the risk stratification tools, how to make a diagnosis and the specific management of stable
patients, critical patients and special populations (e.g., pregnant patients).
Clinical Assessment
Pathophysiology for pulmonary embolism: Why so bad?
Ventilation/perfusion (V/Q) mismatch
Lung parenchyma is ventilated but not getting blood flow or oxygen itself.
Increase pulmonary arterial pressures —> Right heart failure —> Poor coronary artery perfusion
Classic history
DVT symptoms
Painful, swollen, red extremity (see Fig. 1).
PE symptoms
Dyspnea
Approximately 80% of patients with acute PE have shortness of breath.
Fig. 1
Chest pain
Approximately 49% of patients with acute PE have chest pain.
The classic complaint is pleuritic (inspiratory) pain.
Hemoptysis
Can occur but is rare.
Remember the most common cause of hemoptysis is bronchitis.
Syncope
Risk factors
Prior VTE, recent surgery, immobilization, malignancy, OCP use/testosterone supplementation, thrombophilia
Physical
DVT exam findings
Red, swollen, tender unilateral extremity
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May deceptively look similar to cellulitis.
Homan’s sign
Dorsiflexion of foot causes calf tenderness.
Classically taught but not sensitive or specific.
Palpable cord
Tender, indurated, cordlike venous structure
This is a sign of superficial thrombophlebitis, which can be associated with DVT.
A cast on the affected extremity
PE exam findings
Tachypnea
Tachycardia
Only 24-30% of patients will have tachycardia
Hypoxia
Crackles
Fever, cyanosis (less common)
ECG
Classic findings (see table 1)
https://www.emrap.org/episode/ecginpulmonary/ecginpulmonary
Also covered in EMRAP October 2016 by Jeff Kline
https://www.emrap.org/episode/sayhellotobrue/theekginpe
Risk Stratification & Diagnosis
Goals of risk stratification
Decide who does or does not need testing.
Decide what type of testing is appropriate.
Decide who needs empiric treatment.
Spare low risk patients the radiation!
Clinical gestalt
Has the same performance as Wells and Revised Geneva Scores
Caveat: you need clinical experience to have a gestalt.
Pulmonary Embolism Rule-out Criteria (PERC) (see table 2)
To determine if any testing is even needed.
Must start with a low pretest probability (<15% chance) to apply this rule.
If none of the criteria are present and the clinician’s pretest probability is <15%, no further testing is needed.
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If any of the criteria are present then:
Some will order a D-dimer, or follow the PERC rule with a Wells score.
Remember: PERC does not include everything and no decision rule can replace your gestalt.
https://www.emrap.org/episode/december2007/thepercrule
Wells Score (see table 3)
Low, moderate, and high risk groups are determined based on score
Low risk (<2 points)
Some providers will then use the PERC rule, while some will do a D-dimer.
Moderate risk (2-6 points)
Some providers will do a D-dimer, while some will obtain a CT Pulmonary Angiography.
High risk (>6 points)
CT Pulmonary Angiography
Revised Geneva Score
Because there are already so many risk stratification tools, this score is no longer used as frequently. However, it is an
option.
An expert’s approach
Low (<20%): PE Rule Out Criteria (PERC) or D-Dimer
Moderate (21-40%): CT Pulmonary Angiography
High (>40%): Empiric heparin, CT Pulmonary Angiography, and may need additional testing to rule out concurrent DVT
(e.g. extremity ultrasound).
Age adjusted D-dimer
Upper limit for patients over age 50:
Age x 10 for Fibrinogen Equivalent Units (FEUs)
Age x 5 for D Dimer Units (DDUs)
Seems to be an increased specificity without affecting sensitivity
CT pulmonary angiography (CTPA)
Looking for filling defects, signs of right heart failure, or pulmonary infarcts.
Looking for other etiologies of symptoms as well.
Ventilation perfusion (V/Q) scan
Review
Ventilation - patient inhales a benign gas with radioactive isotope (e.g. xenon-133, krypton-81).
Perfusion - technetium-99 is injected and perfusion is assessed.
Need a normal CXR first to evaluate for any possible ventilation defects, then can complete a V/Q scan.
Looks for a mismatch where there is an area of the lung getting ventilated but not perfused, which suggests a blood clot.
Results are categorized into normal, low probability, intermediate probability, and high probability.
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PE Workup In Pregnant Patients
Pregnancy
It is a common myth that pregnant patients have a much higher risk for PE than nonpregnant patients. This myth has
resulted in overtesting of pregnant patients
Most of these epidemiologic studies lumped in DVT with PE and pregnancy with postpartum patients.
Actually proven to have only a very slight increase in risk.
PE occurs in about 3 out of 10,000 pregnancies (averaged over the duration of pregnancy).
Risk is higher:
With DVT
With each trimester
After delivery
With C-section as opposed to vaginal delivery
https://www.emrap.org/episode/springforward/peinpregnancy
Workup
A lot of controversy surrounds the evaluation of PE in pregnancy
D-dimer
Will go up in pregnancy and with each trimester in healthy patients.
If you check a D-dimer and it is negative then that is still reliable for low risk patients, but it is likely to be positive.
Trimester adjusted D-dimer
No validated study to support this although some experts will use 500, 750, and 1,000 as cutoffs for each trimester.
Bilateral lower extremity (BLE) dopplers
DVT is so much more common than PE, and they are treated the same in stable patients.
If you diagnose a DVT then you are done and have caused no radiation.
All chest imaging modalities have their downsides:
CT irradiates the breasts and side effect profile to fetus is not fully known.
V/Q concentrates radioactive isotopes in the bladder right next to the uterus.
Alternatively, clinicians can do just the perfusion scan if the CXR is normal to decrease radiation exposure.
American Thoracic Society (ATS) Guidelines (all based on low quality evidence)
Get BLE ultrasound for DVT if any signs or symptoms of DVT.
If negative, get a CXR next.
If CXR is normal get a V/Q scan.
If CXR is not normal or if V/Q scan is not diagnostic, get a CTPA.
NOTE: ATS does not endorse the use of D-dimer at all (sensitivity is too low).
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Treatment of Stable Patients
Anticoagulation
Direct oral anticoagulation (DOACs)
Options include:
Rivaroxaban or apixaban
Can be started orally immediately with no preceding parenteral anticoagulation.
Dabigatran and edoxaban
Like warfarin, these need parenteral anticoagulation for 5-10 days before starting them.
Choice of DOAC depends on cost/insurance and comorbidities
Some of these are contraindicated if the patient has liver disease.
These are not an option in patients who are on dialysis, pregnant, or breastfeeding.
Low molecular weight heparin (fractionated)
Enoxaparin (and others) - subcutaneous injection
1 mg/kg every 12 hours (pregnancy), or
1.5 mg/kg every 24 hours (not pregnant)
Heparin with a bridge to warfarin, goal INR of 2.0-3.0
Long term plan
May need anticoagulation for 3 months or 6-12 months
Transient risk factors, usually requires 3 months
Persistent risk factors or unprovoked VTE, usually requires 6-12 months
Persistent risk factors and high risk of recurrence may require lifetime anticoagulation
Disposition
Can consider outpatient management if the patient is well-appearing, has good follow up and ability to obtain prescription for anticoagulation.
PE severity index (PESI) and HESTIA criteria
To help decide level of care (who needs admission and who could be discharged safely).
Original and simplified PESI criteria both perform well.
The original classifies more patients as low risk than the simplified PESI.
Choose a score and calculate it, there is a lot of overlap between them.
Lots of risk factors seem fairly obvious (e.g. hemodynamic instability, older age, history of cancer, cardiopulmonary
disease, pregnancy, liver disease, failing outpatient anticoagulation, active bleeding, history of heparin induced
thrombocytopenia, altered mental status).
Ideal patient for discharge: an otherwise healthy patient who clinically looks well, has a small PE, no concerning risk
factors, and is financially and socially able to get their medications and take them reliably.
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Evaluation & Treatment of the Critical Patient
`Ultrasound findings consistent with right heart strain
Due to clot, there are high pressures in the pulmonary arteries, which backs up to the RV causing the following:
RV dilation
On subxiphoid view the normal RV to LV ratio is ⅓ to ⅔. Anything larger (e.g., RV >⅓) is abnormal.
Bowing of the septum into the LV (causing a “D” shaped left ventricle).
https://www.emrap.org/episode/severedsign/severedsign
McConnell’s sign
Akinesia of the RV free wall with normal motion at the apex.
https://www.emrap.org/episode/mcconnellssign/mcconnellssign
Treatment
Fluid resuscitation
Be cautious! Too much fluid can worsen right heart failure and increase bowing into left ventricle
Pressor support
Use pressors like epinephrine or norepinephrine to avoid hypotension and bridge to more definitive therapy.
Anticoagulation
If thrombolysis is potentially possible consider use of unfractionated heparin (half life is only 1-2 hours).
Starting dose is 80 U/kg IV bolus, followed by 16-18 U/kg/hr infusion
Titrate to factor Xa inhibition
If thrombolysis is not possible, use fractionated heparin
Enoxaparin 1 mg/kg SQ
If anticoagulation is contraindicated, consider an IVC filter and start anticoagulation when safe.
Absolute contraindication to anticoagulation
Talk with interventional radiologist or cardiologist about possible clot aspiration.
Thrombolysis
The treatment of choice for massive PE (defined as persistent hypotension lasting >15 minutes due to large embolic
burden).
Check absolute and relative contraindications (see table 4)
Alteplase (FDA approved for PE)
>65 kg: 100 mg IV as a 10 mg IV push followed by 90 mg over 2 hours
<65 kg: adjust to maintain dose <1.5 mg/kg
This is in addition to initiation of anticoagulation with heparin.
Open thrombectomy
Consideration for patients with absolute contraindications to systemic thrombolysis, or as a rescue after failed
systemic thrombolysis.
Consult cardiothoracic surgery if considering.
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Consider ECMO
Nitric oxide
Reduces increased pulmonary vascular resistance from vasoconstriction that happens secondary to clot.
iNOPE trial
Small study
Suggests that patients with acute right heart strain from PE are more likely to resolve their RV dilation or hypokinesis at 24 hours.
Approach to submassive PE with right heart strain
Defined as normotensive but with imaging and biomarkers suggestive of heart strain.
Biomarker findings of right heart strain
BNP >90 pg/mL or pro BNP >900 pg/mL
Troponin - suspected acute elevation above lab reported borderline or higher
Treatment is controversial
Some patients may benefit from thrombolysis, but it isn’t very clear who is an appropriate candidate and what the
appropriate dose of the alteplase should be.
Evaluate risks/benefits, degree of shock/hypoxia, and get consultants involved.
Anticoagulation
References
Garrett J, Kilne J. Venous Thromboembolism. Corependium. Updated: November 3rd 2019. Accessed Nov 3, 2019.
Kline JA, Courtney DM, Kabrhel C, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria.
Journal of Thrombosis and Hemostasis. 2008 May;6(5):772-80. DOI: 10.1111/j.1538-7836.2008.02944.x.
Konstantinides SV, Barco S, Lankeit M,et al. Management of pulmonary embolism: an update. Journal of the American
College of Cardiology. 2016 Mar;67(8):976-90. DOI: 10.1016/j.jacc.2015.11.061.
Meng K, Hu X, Peng X, et al. Incidence of venous thromboembolism during pregnancy and the puerperium: a systematic
review and meta-analysis. The Journal of Maternal-Fetal & Neonatal Medicine. 2015 Feb;28(3):245-53.
DOI: 10.3109/14767058.2014.913130.
Minati M, Prediletto R, Formichi B, et al. Accuracy of clinical assessment in the diagnosis of pulmonary embolism. American
Journal of Respiratory Critical Care Medicine. 1999 Mar;159(3):864-71. DOI: 10.1164/ajrccm.159.3.9806130.
Prandoni P, Lensing AW, Prins MH, et al. Prevalence of pulmonary embolism among patients hospitalized for syncope. New
England Journal of Medicine. 2016 Oct;375:1524-1531. DOI: 10.1056/NEJMoa1602172.
Rezaie S. Age adjusted D-dimer testing. RebelEM Web site. https://rebelem.com/age-adjusted-d-dimer-testing/. Published
April 28, 2014. Accessed June 12, 2019.
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Righini M, Robert-Ebadi H, Elias A, et al. Diagnosis of Pulmonary Embolism During Pregnancy: A Multicenter Prospective
Management Outcome Study. Ann Intern Med. 2018 Dec;169(11):766-773. DOI: 10.7326/M18-1670.
Tapson V, Weinberg A. Treatment, prognosis, and follow-up of acute pulmonary embolism in adults. UptoDate Web site.
https://www.uptodate.com/contents/treatment-prognosis-and-follow-up-of-acute-pulmonary-embolism-in-adults?search=pulmonary%20embolism&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2.
Updated May 16, 2019.
Thiruganasambandamoorthy V, Sivilotti ML, Rowe BH, et al. Prevalence of Pulmonary Embolism Among Emergency
Department Patients With Syncope: A Multicenter Prospective Cohort Study. Annals of Emergency Medicine. 2019 May;
73(5):500-510. DOI: 10.1016/j.annemergmed.2018.12.005.
Venetz C, Jiménez D, Méan M, et al. A comparison of the original and simplified Pulmonary Embolism Severity Index.
Thrombosis and Hemostasis. 2011 Sep;106(09):423-8. DOI: 10.1160/TH11-04-0263.
Wells PS, Anderson DR, Rodger M, et al. Excluding Pulmonary Embolism at the Bedside without Diagnostic Imaging: Management of Patients with Suspected Pulmonary Embolism Presenting to the Emergency Department by Using a Simple
Clinical Model and d-dimer. Ann Intern Med. 2001 Jul;135(2):98–107. DOI: 10.7326/0003-4819-135-2-200107170-00010.
Wilbur J, Shia B. Diagnosis of deep venous thrombosis and pulmonary embolism. Am Fam Physician. 2012 Nov;86(10):913-9.
PMID: 23157144
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Table 1: ECG Findings in Pulmonary Embolism
Nonspecific ECG changes
Sinus tachycardia
Right axis deviation
Right bundle branch block
S1Q3T3 (uncommon)
T wave inversion in the anterior leads (Wellens pattern)
ST elevation in aVR
Atrial fibrillation
Table 2: PERC Criteria*
Age ≥50
Heart rate ≥100 at triage
Oxygen saturation <95%
Unilateral leg swelling
Hemoptysis
Recent surgery or trauma
≤4 weeks, requiring general anesthesia
Prior PE or DVT
Hormone use
Oral contraceptives, hormone replacement therapy,
or estrogen use
Table 3. Wells Score*
Criteria
Clinical signs and symptoms of DVT
(objectively measured leg swelling and calf
tenderness)
Heart rate >100
Immobilization (bedrest except access to
bathroom for ≥3 consecutive days)
Or surgery in previous 4 weeks
Previously diagnosed DVT or PE
Hemoptysis
Malignancy
PE is #1 diagnosis or equally likely
Points
3
1.5
1.5
1.5
1
1
3
Score <2 = low risk (1.3% prevalence)
Score 2-6 = moderate risk
Score >6 = high risk
* Adapted from Wells, 2001
If none of the criteria are present and the clinician’s pretest probability is
<15%, no testing is needed.
* Adapted from Kline, 2008
Table 4. Absolute and Relative Contraindications for IV thrombolysis in PE
Absolute Contraindications for IV thrombolysis in PE
Prior intracranial hemorrhage
Known intracranial neoplasm, AVM, or aneurysm
Within previous 3 months:
Ischemic stroke
GI bleed
Active bleeding at a non-compressible site
Known bleeding diathesis
Liver failure with INR >1.7
Within previous 21 days:
Surgery or invasive procedure requiring the opening of
the chest, peritoneum, skull, or spinal canal
Significant trauma
Relative Contraindications for IV thrombolysis in PE
Recent bleeding
Within previous 22-90 days:
Surgery or invasive procedure
Ischemic stroke within 3-12 months
Symptoms suggesting TIA in past 6 months
Traumatic cardiopulmonary resuscitation
Pericarditis or pericardial fluid
Diabetic retinopathy
Pregnancy
Age > 75 years
Any metastatic cancer
Any prior GI bleeding
* adapted from Garrett J (2019),
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