2. 2
GoalsGoals
Understand the historical context of pulmonary emboli
Comprehend the pathophysiology and know some common
risk factors
Be aware of the clinical features of PE and have a basic
understanding of various diagnostic tests
Gain a therapeutic approach to the treatment of PE and
discuss a simplified method in the work-up of PE
Attempt to dispel a few “myths”about pulmonary emboli
3. 3
PerspectivePerspective
A Common disorder and potentially deadly
650,000 cases occurring annually
Highest incidence in hospitalized patients
Autopsy reports suggest it is commonly “missed”
diagnosed
4. 4
PerspectivePerspective
Presentation is often “atypical”
Signs and symptoms are frequently vague and
nonspecific and rarely “classic”
Untreated mortality rate of 20% - 30%,
plummets to 5% with timely intervention
7. 7
So What Do We Do ???So What Do We Do ???
Confusing for Physician
Do we under diagnose/over diagnose?
Why don’t we have a standardized method of
work up after all these years?
9. 9
Risk FactorsRisk Factors
Hypercoagulability
Malignancy
Nonmalignant thrombophilia
Pregnancy
Postpartum status (<4wk)
Estrogen/ OCP’s
Genetic mutations (Factor V Leiden, Protein C & S deficiency, Factor
VIII, Prothrombin mutations, anti-thrombin III
deficiency)
Venous Statis
Bedrest > 24 hr
Recent cast or external fixator
Long-distance travel or prolong automobile travel
Venous Injury
Recent surgery requiring endotracheal intubation
Recent trauma (especially the lower extremities and pelvis)
10. 10
Clinical PresentationClinical Presentation
The Classic Triad: (Hemoptysis, Dyspnea, Pleuritic
Pain)
Not very common!
Occurs in less than 20% of patients with documented PE
Three Clinical Presentations
– Pulmonary Infarction
– Submassive Embolism
– Massive Embolism
12. 12
Mythology of PEMythology of PE
Myth
– “Patients with pulmonary embolism are short of
breath and have chest pain!”
Reality:
You can forget about making the diagnosis on
clinical grounds, but wait…don’t plan on completely
ruling it out either!
15. 15
Who do we work up?Who do we work up?
-- Pretest ProbabilityPretest Probability
Definition: “The probability of the target
disorder (PE) before a diagnostic test
result is known”.
Used to decide how to proceed with
diagnostic testing and final disposition
“Guess”
– This is really what it boils down to!
17. 17
Diagnostic TestingDiagnostic Testing
- CXR’s- CXR’s
Chest X-Ray Myth:
“You have to do a chest x-ray so you can find
Hampton’s hump or a Westermark sign.”
Reality:
Most chest x-rays in patients with PE are
nonspecific and insensitive
18. 18
Diagnostic TestingDiagnostic Testing
-- CXR’sCXR’s
Chest radiograph findings in patient with
pulmonary embolism
Result Percent
Cardiomegaly 27%
Normal study 24%
Atelectasis 23%
Elevated Hemidiaphragm 20%
Pulmonary Artery Enlargement 19%
Pleural Effusion 18%
Parenchymal Pulmonary Infiltrate 17%
19. 19
Chest X-ray Eponyms of PEChest X-ray Eponyms of PE
Westermark's sign
– A dilation of the pulmonary vessels proximal to the
embolism along with collapse of distal vessels,
sometimes with a sharp cutoff.
Hampton’s Hump
– A triangular or rounded pleural-based infiltrate with
the apex toward the hilum, usually located adjacent to
the hilum.
21. 21
Diagnostic TestingDiagnostic Testing
– ECG’s– ECG’s
ECG
– Most Common Findings:
Tachycardia or nonspecific ST/T-wave changes
– Acute Cor Pulmonale or right strain patterns
Tall peaked T-waves in lead II (P Pulmonale)
Right axis deviation
RBBB
S1-Q3-T3 (Occurs in only 20% of PE patients)
22. 22
Diagnostic TestingDiagnostic Testing
-- Pulse OximetryPulse Oximetry
The Pulse Oximetry Myth:
– “ You must do a pulse oximetry reading, since
patients with pulmonary embolism are hypoxemic!”
Reality:
– Most patients with a PE have a normal pulse
oximetry, and most patients with an abnormal pulse
oximetry will not have a PE.
23. 23
Diagnostic TestingDiagnostic Testing
- ABG’s- ABG’s
The ABG/ A-a Gradient myth:
– “You must do an arterial blood gas and calculate the alveolar-
arterial gradient. Normal A-a gradient virtually rules out PE”.
Reality:
– The A-a gradient is a better measure of gas exchange than the
pO2, but it is nonspecific and insensitive in ruling out PE.
25. 25
Ancillary TestAncillary Test
WBC
– Poor sensitivity and nonspecific
Can be as high as 20,000 in some patients
Hgb/Hct
– PTE does not alter count but if extreme, consider
polycythemia, a known risk factor
ESR
– Don’t get one, terrible test in regard to any predictive
value
26. 26
D-dimer TestD-dimer Test
Fibrin split product
Circulating half-life of 4-6 hours
Quantitative test have 80-85% sensitivity, and 93-100% negative
predictive value
False Positives:
Pregnant Patients Post-partum < 1 week
Malignancy Surgery within 1 week
Advanced age > 80 years Sepsis
Hemmorrhage CVA
AMI Collagen Vascular Diseases
Hepatic Impairment
27. 27
Diagnostic TestingDiagnostic Testing
D-dimer
– Qualitative
Bed side RBC agglutination test
– “SimpliRED D-dimer”
– Quantitative
Enzyme linked immunosorbent asssay “Dimertest”
Positive assay is > 500ng/ml
VIDAS D-dimer, 2nd
generation ELISA test
28. Plasma D-dimer ELISAPlasma D-dimer ELISA
usefull diagnostic approach
Sensitive but nonspecific test for PE
High negative predictive value when
concentration is <500 ng/mL
Can help reduce frequency of pulmonary
angiography
Diagnostic strategy of V/Q scanning plus
29. 29
Ventilation/Perfusion ScanVentilation/Perfusion Scan
- “V/Q Scan”- “V/Q Scan”
A common modality to image the lung and its
use still stems from the PIOPED study.
Relatively noninvasive and sadly most often
nondiagnostic
In many centers remains the initial test of choice
Preferred test in pregnant patients
50 mrem vs 800mrem (with spiral CT)
30. 30
V/Q ScanV/Q Scan
Technique
Interpretation
– Normal
– Low probability/”nondiagnostic” (most common)
– High Probability
Simplified approached to the interpretation of results:
High probability Treat for PE
Normal Scan If low pre-test, you are done
Everything else Pursue another study (CT, Angio)
36. 36
Treatment:Treatment:
Goals:
Prevent death from a current embolic event
Reduce the likelihood of recurrent embolic
events
Minimize the long-term morbidity of the event
Dr. T.M.K explaining
the CT results
Patient
replies:
“Uh-huh,
when do I
get to eat!”
37. 37
TreatmentTreatment
Anticoagulants
– Heparin
Provides immediate thrombin inhibition, which prevents
thrombus extension
Does not dissolve existing clot
Will not work in patients with antithrombin III def.
– In this case use hirudins
Few absolute contraindications
38. 38
TreatmentTreatment
Anticoagulants
– Heparin
Available as Unfractionated or LMW Heparin
– FDA approved dosing:
• Unfractionated: 80 units/kg bolus, 18 units/kg/Hr
• LMWH: 1 mg/kg Q 12 or 1.5mg/kg Q D
LMWH preferred in pregnant patients
39. 39
TreatmentTreatment
Anticoagulants
– Warfarin (Coumadin)
Interferes with the action of Vit-K dependent factors: II, VII,
IX, and X, as well as protein C & S
Causes temporary hypercoagulable state in first 5 days of
treatment
– Important a patient is anticoagulated with heparin before
initiating warfarin therapy
Target INR is 2.5 – 3.0
40. 40
TreatmentTreatment
Fibrinolytic Therapy (Alteplase)
– Indications:
Documented PE with:
– Persistent hypotension
– Syncope with persistent hemodynamic compromise
– Significant hypoxemia
– +/- patient with acute right heart strain
Approved regimen is 100mg as a continuous IV infusion
over 10 minutes for critically ill patients.
43. 43
A Simplified AlgorithmA Simplified Algorithm
Pre-test probability
D-dimer
CT angiography
Low Pre-test, D-dimer (-),
patient had < 1.7% 90 day
PE occurrence in a Mayo
Clinic Study
44. 44
Special CircumstancesSpecial Circumstances
Morbid Obesity
Pregnancy
V/Q has considerable less radiation
– 50 mrem vs. 800 mrem
Almost all will have positive D-Dimer
Heparin safe in pregnancy
Witnessed Cardiac Arrest
Standard ACLS, if known PE, the lytics.
45. Recommendations
Duration of therapy
First thromboembolic event in the context of a reversible
risk factor
-- Treated for three to six months
Idiopathic first thromboembolic event
-- AT LEAST full six months of treatment
-- Further therapy at discretion of clinician
Recurrent venous thrombosis or a continuing risk factor --
Treated indefinitely.
46. Adverse events and clinicalAdverse events and clinical
outcomeoutcome
Recurrent PE
Death
Bleeding Complications:
Intracranial bleed
Pulmonary hypertension
50. 50
1. Which of the following is not a part of
virchows triad?
a) Hypercoagulability
b) Stasis to flow
c) Vessel injury
d) History of previous DVT
51. 51
2. Which of the following is the propper
treatment of fat emboli?
a) Platelets
b) High dose steroids
c) Heparin
d) cryoprecipitate
52. 52
3. The Classic Triad of patients presenting
to the ED with PE includes all of the
following except:
a) Hemoptysis
b) Dyspnea
c) + Homans’ sign
d) Pleuritic Pain
53. 53
4. What is the most common
symptom in a patient with Angio
Proven PTE?
a) Dyspnea
b) Chest Pain, pleuritic
c) Anxiety
d) Cough
54. 54
5. What is the most common ecg finding in
patients with PE?
a) Right axis deviation
b) RBBB
c) S1-Q3-T3
d) Tall peaked T-waves in lead II (P pulmonale)
e) Sinus tachycardia
56. 56
ConclusionConclusion
Summary PointsSummary Points
Pulmonary Emboli remain a potentially deadly and common event whichPulmonary Emboli remain a potentially deadly and common event which
may present in various waysmay present in various ways
Don't’ be fooled if your patient lacks the “classic” signs and symptoms!Don't’ be fooled if your patient lacks the “classic” signs and symptoms!
Consider PE in any patient with an unexplainable cause of dyspnea,Consider PE in any patient with an unexplainable cause of dyspnea,
pleuritic chest pain, or findings of tachycardia, tachpnea, or hypoxemiapleuritic chest pain, or findings of tachycardia, tachpnea, or hypoxemia
22ndnd
Generation Qualitative D-Dimers have NPV of 93-99%Generation Qualitative D-Dimers have NPV of 93-99%
Heparin remains the mainstay of therapy with the initiation of WarfarinHeparin remains the mainstay of therapy with the initiation of Warfarin
to followto follow
Simplified Algorithm: ( Pretest probability, D-Dimer, +/- CT angio), thenSimplified Algorithm: ( Pretest probability, D-Dimer, +/- CT angio), then
disposition)disposition)
I mention here that PE is an elusive diagnosis. More than 25 years often Eugene Robin wrote a landmark article on the diagnosis and management of PE, even today, we still are puzzled over the best approach to this clinical entity. So, lets take a few minutes and go over the goals of this topic.
So let us begin
Pulmonary embolism is the most serious complication of venous thrombosis It is the third most common cause of death in the US As many as 60% of deaths in hospitalized patients are found to have pulmonary emboli So, generally speaking it is a hard diagnosis to make…. As clinicians we must consider the diagnosis in patients to put us on the right path
PE It has a wide spectrum of patient presentation, which leads us to do suboptimal testing. This can stand in the way of a timely diagnosis It’s important, because prompt diagnosis and treatment can dramatically reduce the mortality rate and morbidity of this disease. Unfortunately, the diagnosis is missed far more than it is made. I want to offer you a historical perspective of the disorder
Until the 1930’s, PTE was viewed almost universally fatal, with surgery the only treatment despite an operative mortality of 100% Enter heparin, circa 1930’s, heparin was discovered and its wide spread use were so immediate and dramatically apparent that this become the mainstay of treatment for the next 70 years! In 1977, a physician be the name of Eugene Robin published a landmark article which stimulated immense change in medicines approach to diagnosing PE. It was robin contention the while lung scintigraphy was sensitive to the presence of clots, but also non-specific. He questioned the value of ventilation scans when the perfusion defects were small. He felt angiography was being underused, and that PE….was being OVER diagnosed.
Jump ahead to 1990. The PIOPED investigators, stimulated by Robins article published their data on the sensitivities and specificities of V/Q scans for PE. In summary, a random sample of 933 of 1493 patients were studied prospectively. 931 had scintography and 755 underwent angiography. Their conclusion: clinical assessment combined with the V/Q scan can establish the diagnosis or exclusion of pulmonary embolism only for a minority of patients Enter the electronic era, Craig Feied, MD, who has read every published article about PE written in the last 100 years and who has written the chapter in Rosen’s in the last two editions published this statement: Massive PE is one of the most common causes of unexpected death, being second only to coronary artery disease as a cause of sudden unexpected natural death at any age. Most clinicians do no appreciate the extent of the problem, because the diagnosis is unsuspected until autopsy in approximately 80% of cases.
Do we under diagnose or over diagnose? If we over diagnose, is it such a big deal? It’s just a few month of inconvenience of heparin and warfarin. Aside from the potential morbidity of the anticoagulants,there are other problems. The diagnoses carries a stigma which will contaminate all future medical encounters. Women may be barred from oral contraceptives, future pregnancies will be considered high risk. Elective surgery may be denied. So, really after all these years, we are still left in the dark. We still don’t have a collective conscience on a standard approach to this problem. Before we can answer any questions we have to understand the condition and this take us to virchow.
Everyone I’m sure is familiar with Virchow’s triad. It was first described by this German pathologist. If we think of risk factors, we should think of them as the embodiment of the triad: hypercoagulability, stasis, and vessel injury. So, essentially, under normal conditions, microthrombi are continually formed and lysed with the venous circulatory system. When any one of the “risk states” exists, potential microthrombi may escape the normal fibrinolytic system and grow and propagate. Pulmonary Emboli occurs when fragments of thrombus break loose and are carried through the right side of the heart into the pulmonary arterial tree.
Cancers of primarily adenocarcinoma and CNS tumors most often cause thrombosis. We need to make special mention about patients with a prior history of DVT or PE. Studies have revealed these patients have between a 5 to 30 times increased risk of a new DVT in response to a triggering event compared to those who have not had prior episodes.
All the above symptoms are a manifestation of cardiopulmonary stress caused by the cloth in the lung. These produce symptoms perceived by the patient and the signs observed by you! There are three common clinical presentations that you should be aware of: 1. Patient’s with pulmonary infarction may have pleuritic chest pain and can be hard to distinguish between that patient with infection pneumonitis 2. Submassive embolism are the hardest of all. By definition, they have an angiographically defined blockage of flow to an area served by less than two lobar arteries. These patients have acute or unexplained dyspnea with exertion or at rest. So, they can be easily confused with infection, asthma, CHF and the like. 3. Finally, Massive PE, or a clot which obstructs two lobar arteries, so-called “Saddle Embolus”. These patients have acute cor pulmonaly often with syncope. You might think there having an MI or look septic!
While it’s true the most common symptom is shortness of breath, even patients with circulatory collapse may have no dyspnea, tachypnea, or pleuritic pain! In fact, A normal paO2 > 80 is more prevalent in patients with pulmonary infarction syndrome. As a simple rule, if you have a patient in your department and you don’t have a good reason to explain there dyspnea, it’s a good idea to consider PE!
These are the common symptoms that are associated with PE As we mentioned in the previous slide, dyspnea and chest pain are not always preset. The explanation is that with a small V/Q mismatch, the adaptive physiology of the pulmonary vasculature and bronchi produce intermittent shortness of breath. Because of this, we are easily distracted and looking for a cardiogenic cause of the dyspnea. What about pleuritic chest pain, still not a home run! In fact, up to 25% of patients ultimately diagnosed with a PE, never had any chest pain! This is what makes the diagnosis so difficult!
Lets look a t a couple of these: Tachycardia! Myth #2 We are all taught this is a key component of the diagnosis. Right? In fact, actually not having tachycardia is more commonly seen in patients who are found to have a PE! What about fever? If a patient has a fever, it must not be a PE, right? Not true. Although not common, Among patients with PE and no other source of fever, fever was present in one study in 43 of 311 patients (14%).
For example This could represent the likelihood that a specific patient , say a middle-aged man, with a specific past history, say hypertension and tobacco smoking who presents with a specific symptom complex: Chest pain, Dsypnea, or Diaphoresis has a specific diagnosis. Final Statement: Because PE can present with or with any of the “classic signs and symptoms” and even the risk factors which contribute to PE are varied in frequency, we are left with a intuition at best!
As you can see there are a variety of test that we use to arrive at a diagnosis. Some better than others! So, lets talk about these individually.
Granted that most are abnormal, but certainly not diagnostic. It is true that in the original PIOPED study it was recommended but the main value is to exclude diagnoses the mimic PE and to aid in the interpretation of the V/Q scan
Cardiomegaly was the most frequent finding in those with PE of In-patients Out-patients , it seemed to be atelectasis in the above study.
Here we see the dilated vessels and oligemia of westermark’s sign And below Hampton’s Hump
A brief mention about the classic S1-Q3-T3, its appearance on the EKG may suggest PE, but study after study has shown it has no predictive value what so ever! But you got to know it because question writers for the boards love it!
Actually, it is opposite of what you might think!
As with most dogma, we are taken back by what we thought was truth. About 15% of patients with proven pulmonary embolism have a pO2 of 85mmHg or higher! In one study, researches drew from there data various combinations of the PaO2 of 80mm Hg or more, the PaCO2 of 35mmHg or higher, and the A-a gradient of 20 mmHg or less. They found that PE could not be excluded in more than 30% of patients with no prior cardiopulmonary disease. Moreover, PE could not be excluded in more than 14% of patients with prior cardiopulmonary disease. Conclusion, Blood gas levels are poor discriminate value to permit the exclusion of PE.
Diagnosing of early right ventricular strain is important because it is a strong predictor of subsequent death Important to recommend echocardiogram with your admitting internist if a pattern of right heart strain is suggested by EKG. Studies have documented that lives are saved with early fibrinolysis is considered in these patients.
Well, what is it? Basically, the assay is enzyme-linked monoclonal antibody test used to identify the protein, D-Dimer. D-Dimer itself is a unique degradation product that is produced by a plasmin mediated breakdown of cross-linked fibrin Good test with respect to its negative predictive value. The drawbacks are some of the false positives that we commonly see in the ER.
Two types, Qualitative RBC agglutination assay, low sensitivity and specificity and not good enough to comfortably rule out PE. Quantitative , which measure the accurately the amount using a spectrophotometer. Our lab uses the 2 nd generation VIDAS d-dimer with a negative predictive value of 99.3%!
Essentially, a patient is injected with a radioisotope that travels through the pulmonary microcirculation and are detected by a gamma camera over the patient A normal Perfusion study will have evenly distributed blood flow. Then a patient inhales a radioactive gas and it is viewed as it washes over the bronchopulmonary tree. A mismatch, areas of blocked perfusion and normal ventilation is interpreted by the radiologist and given reading as normal (never), high probability, or non-diagnostic/low-probability The reason the low probability or non diagnostic scan category is so suspect is because in the PIOPED study this group had terrible inter-reader reliability. So, just beware.
Intro: Pulmonary Embolus Training Week April 2005
The entire lung can be scanned while the patient holds there breath. Advantages: CT most useful benefit is in providing evidence for an alternative diagnosis or excluding it entirely. Disadvantages: The clinical significance for subsegmental PE are not well known, but may be a marker for a larger PE Given that the majority of V/Q studies are non-diagnostic, I prefer the CT as the initial test of choice in place of V/Q scan.
Intro: Pulmonary Embolus Training Week April 2005
Right now there is no better test on the horizon of the immediate present to virtually rule out or in PE.
Intro: Pulmonary Embolus Training Week April 2005
I thought this cartoon kind of summarizes how patients sometimes feel about the medical jargon we throw about and the puzzled look are there face when we try to explain this condition and how to treat it. So what are our goals???
Heparin is the most frequently used drug in the treatment of PE. Because heparin works by activating antithrombin III, this genetic mutation makes heparin ineffective.
FDA approved dose for Unfractionated heparin is 80units/kg IV bolus, then 18 units/kg/hr infusion to maintain the INR at 2.5-3 Lovenox is dosed at 1mg/kg every 12 hours or 1.5 mg/kg per day. LMWH in pregnancy only preferred for convenience sake.
This is because the anticoagulants protein C and S have short half-lives compared with the procoagulant vitamin K-dependent proteins. So, this gives rise to the clinical importance that heparin must be continued for at least five days after beginning Coumadin The incidence of progressive thrombosis and embolization is 40% when starting warfarin directly, compared to only 8% when beginning after a patient has been anticoagulated with heparin. Treatment is usually for 6 months, but may continue lifelong
For critically ill patients, a very rapid infusion of 100mg over 10 minutes is preferred. Alternative is Retavase, you can give it as two IV doses of 10 units, each over two minutes.
This is a procedure where a suction tip catheter is placed in contact with the thrombus under fluoroscopy and sucked out while catheter is withdrawn
The simplest algorithm says you can safely rule out PE in a low pre-test patient with a negative D-dimer I believe our institution and my personal practice is similar to the Mayo Clinic Group who uses a combination of pre-test probability, D-dimers, and CT angio, and limited V/Q to arrive at a disposition.
These patients are difficult if not impossible to image. D-dimer may be useful if < 500 and you can support an alternative diagnosis. Pregnant patients