You are on page 1of 48

 PULMONARY EMBOLISM

B.GANGADHAR
PULMONARY EMBOLISM

• Pulmonary embolism (PE) refers to exogenous or
endogenous material that travels to the lungs through
the pulmonary circulation, causing a potential spectrum
of consequences.

• Thrombus from the deep veins of the lower extremities is
by far the most common material to embolize to the
lungs

• Tumor cells, air bubbles, carbon dioxide, intravenous
catheters, fat droplets, and talc in intravenous drug
abusers are also potential sources of emboli.
PULMONARY EMBOLISM

• Genetic and acquired factors contribute to the likelihood of
VTE.

• The two most common autosomal dominant genetic
mutations are the factor V Leiden and the prothrombin
gene mutations

• However, only a minority of patients with VTE have
identifiable predisposing genetic factors. The majority of
patients with predisposing genetic factors will not
develop clinical evidence of clotting
Major Acquired Risk Factors

• Advancing age
• Arterial disease including carotid and coronary disease
• Obesity
• Cigarette smoking
• Chronic obstructive pulmonary disease
• Personal or family history of venous thromboembolism
• Recent surgery, trauma, or immobility including stroke
• Acute infection
• Long-haul air travel
• Cancer Pregnancy, oral contraceptive pills, or hormone
replacement therapy
• Pacemaker, implantable cardiac defibrillator leads, or
indwelling central venous catheters


Major Thrombophilias Associated with VTE

• Inherited Factor V Leiden resulting in activated protein C
resistance
• Prothrombin gene mutation 20210
• Antithrombin III deficiency
• Protein C deficiency
• Protein S deficiency
• Acquired Antiphospholipid antibody syndrome
• Hyperhomocysteinemia
Pathophysiology

 Embolization :

• About half of patients with pelvic vein thrombosis or
proximal leg DVT develop PE, which is usually
asymptomatic.

• Isolated calf vein thrombi pose a much lower risk of PE, but
they are the most common source of paradoxical
embolism.

• With increased use of chronic indwelling central venous
catheters, permanent pacemakers and internal cardiac
defibrillators, upper extremity venous thrombosis is
becoming a more common problem. These thrombi
rarely embolize and cause PE.

Physiology

• The most common gas exchange abnormalities are
hypoxemia (decreased arterial PO2 ) and an increased
alveolar-arterial O2 tension gradient.

• Anatomic dead space increases because breathed gas does
not enter gas exchange units of the lung.

• Physiologic dead space increases because ventilation to gas
exchange units exceeds venous blood flow through the
pulmonary capillaries.
 Other pathophysiological abnormalities include:

• Increased pulmonary vascular resistance due to vascular
obstruction or
 platelet secretion of vasoconstricting neurohumoral
agents such as serotonin.

• Impaired gas exchange due to increased alveolar dead
space

• Alveolar hyperventilation due to reflex stimulation of irritant
receptors

• Increased airway resistance due to constriction of airways
distal to the bronchi

• Decreased pulmonary compliance due to lung edema, lung
hemorrhage, or loss of surfactant
Right Ventricular Dysfunction
CLINICAL PRESENTATION
 Clinical Decision Rule

• >4 score points = high probability  
 ≤4 score points = non–high probability    

Score Points
• DVT symptoms or signs 3
• An alternative diagnosis is less likely than PE 3
• HR > 100/min
1.5
• Immobilization or surgery within 4 wk 1.5
• Prior DVT or PE 1.5
• Hemoptysis 1
• Cancer treated within 6 mo or metastatic 1

DIFFERENTIAL DIAGNOSIS.

 Myocardial infarction
Pericarditis
Heart failure
Pneumonia
Asthma
Chronic obstructive pulmonary disease
Pneumothorax
Pleurodynia
Pleuritis from connective tissue disease
Thoracic herpes zoster (“shingles”)
Rib fracture
Musculoskeletal pain
Primary or metastatic intra thoracic cancer
Infra diaphragmatic processes (e.g., acute cholecystitis,
splenic infarction)
Hyperventilation syndrome
Clinical Syndromes of Pulmonary
Embolism
• Classification of Acute Pulmonary Embolism :
Classification Presentation
Therapy
Massive PE Systolic BP ≤ 90 mm Hg
Thrombolysis
 or poor tissue perfusion or
embolectomy
 or multisystem organ failure or
IVC filter
 plus
plus
 rt or ltPA thrombus
anticoagulation
 or “high clot burden”
SubmassivePE Hemodynamically stablebut
Addition of thrombolysis,
 mod. or sev.RVdysfunction
Clinical Syndromes of Pulmonary Embolism

• PULMONARY INFARCTION.
 Caused by a tiny peripheral pulmonary embolism
 Tissue infarction usually occurs 3 to 7 days after
embolism.
 Pleuritic chest pain, often not responsive to
narcotics
 Low-grade fever
 Pleural rub
 Occasional scant hemoptysis
 Leukocytosis
• PARADOXICAL EMBOLISM.
 small DVT that embolizes to the arterial system,
usually through a

patent foramen ovale.
Clinical Syndromes of Pulmonary Embolism

 NONTHROMBOTIC PULMONARY EMBOLISM:
 include fat, tumor, air, and amniotic fluid

 -Fat embolism syndrome is most often observed after
blunt trauma
 complicated by long-
bone fractures.

 -Air embolus can occur during placement or removal of
CVC

 - Amniotic fluid embolism may be catastrophic and is
characterized by
 respiratory failure,
cardiogenic shock, and DIC.
Nonimaging Diagnostic Modalities

PLASMA d-DIMER ASSAY:

• Quantitative plasma D-dimerenzyme-linked immunosorbent
assay (ELISA) rises in the presence of DVT or PE .
• The sensitivity of the D-dimer is greater than 95% for PE.
• The D-dimer is a useful "rule out" test. It is normal (<500
ng/mL) in more than 95% of patients without PE.
• In patients with low clinical suspicion of DVT, it is normal in
more than 90% without DVT.
• The D-dimer assay is not specific.
• Levels increase in pts with MI, pneumonia, sepsis, cancer,
the postoperative state, and 2nd or 3rd trimester of
pregnancy.
• Therefore, it rarely has a useful role among hospitalized
patients because their D-dimers are frequently elevated
due to some systemic illness

Nonimaging Diagnostic Modalities

• Elevated Cardiac Biomarkers :
 -Serum troponin levels increase in RV microinfarction.

 -Myocardial stretch often results in elevation of BNP or
NT-pro- BNP

 -Elevated cardiac biomarkers predict an increase in
major
 complications and mortality
from PE

ELECTROCARDIOGRAM.
 -Sinus tachycardia

 - Incomplete
orcompleteRBBB
 - Right axis deviation

 -T wave inversions in
leads III and aVF or in
leads V1-V4

 -S wave in lead I and a
Q wave and T wave
inversion in lead III
(S1Q3T3)

 -QRS axis >90 degrees
or an indeterminate
Noninvasive Imaging Modalities

 CHEST RADIOGRAPHY :
 -A normal or near-normal CXR in a dyspneic patient
often occurs in PE.
 -Well-established abnormalities include

 focal oligemia( Westermark's sign),

 a peripheral wedged-shaped density above
the diaphragm

(Hampton's hump), or

 an enlarged right descending pulmonary
artery ( Palla's sign).

Chest CT
• CT of the chest with IV contrast is the principal imaging test
for the diagnosis of PE.

• Multi detector-row spiral CT acquires all chest images with 1
mm .This CT scanners can image small peripheral
emboli.

• The CT scan also obtains excellent images of the RV and LV
and can be used for a risk stratification as well as a
diagnostic tool.

• In patients without PE, the lung parenchymal images may
establish alternative diagnoses not apparent on chest x-
ray that explain the presenting symptoms and signs,
such as pneumonia, emphysema, pulmonary fibrosis,
pulmonary mass, or aortic pathology.
Lung Scanning
• Lung scanning is now a second-line diagnostic test for PE.
• It is mostly used for patients who cannot tolerate
intravenous contrast.
• Small particulate aggregates of albumin labeled with a
gamma-emitting radionuclide are injected IV and are
trapped in the pulmonary capillary bed.

• The perfusion scan defect indicates absent or decreased
blood flow, possibly due to PE.

• Ventilation scans, obtained with radiolabeled inhaled gases
such as xenon or krypton, improve the specificity of the
perfusion scan.

• Abnormal ventilation scans indicate abnormal non
ventilated lung, thereby providing possible explanations
for perfusion defects other than acute PE, such as
asthma or COPD.

Lung Scanning

• A high probability scan for PE is defined as having two or
more segmental perfusion defects in the presence of
normal ventilation.

• The diagnosis of PE is very unlikely in patients with normal
and near-normal scans but is about 90% certain in
patients with high-probability scans.

• As many as 40% of patients with high clinical suspicion for
PE and "low-probability" scans do, in fact, have PE at
angiography.
Magnetic Resonance (MR)

• MR utilizes gadolinium contrast agent, which, unlike
iodinated contrast agents used in venography or CT
angiography, is not nephrotoxic.

• MR imaging should be considered for suspected DVT or PE
patients with renal insufficiency or contrast dye allergy.

• MR pulmonary angiography detects large proximal PE but is
not reliable for smaller segmental and sub segmental PE.
Echocardiography
• Echocardiography is not a reliable diagnostic imaging tool
for acute PE.

• Transthoracic echo. rarely images thrombus directly.
 The best-known indirect sign of PE on transthoracic
echo. is
 McConnell's sign, hypokinesis of the RV free wall
with normal
 motion of
the RV apex.

• Transesophagealecho should be considered when CT
scanning facilities are not available or when a patient has
renal failure or severe contrast allergy.
 This imaging modality can directly visualize
large proximal PE.
VENOUS ULTRASONOGRAPHY

• The primary diagnostic criterion for DVT is loss of vein
compressibility. Normally, the vein collapses completely
when gentle pressure is applied to the skin overlying it.

• When PE is suspected, venous ultrasonography is useful if
it demonstrates DVT because DVT can be considered a
surrogate for PE.

• However, at least half of patients with PE have no imaging
evidence of DVT.

• Therefore if clinical suspicion of PE is moderate or high,
patients without evidence of DVT should undergo further
investigation for PE.
Invasive Diagnostic Modalities

 Pulmonary Angiography :
 -Chest CT with contrast has virtually replaced invasive
pulmonary angiography as a diagnostic test.

 - reserved for patients with technically unsatisfactory chest
CTs or for those in whom an interventional procedure such
as catheter-directed thrombolysis or embolectomy is
planned.

 - A definitive diagnosis of PE depends upon visualization of
an intraluminal filling defect in more than one projection.

 -Secondary signs of PE include abrupt occlusion ("cut-off")
of vessels, segmental oligemiaor avascularity, a prolonged
arterial phase with slow filling, or tortuous, tapering
peripheral vessels
Invasive Diagnostic Modalities

• Contrast Phlebography

 Venous ultrasonography has virtually replaced contrast
phlebography as the diagnostic test for suspected DVT.


Integrated diagnostic approach
MANAGEMENT
MANAGEMENT
Risk Stratification
Predictors of Increased Mortality

• Clinical
 Systolic blood pressure less than or equal to 100 mm Hg
 Age older than 70 years
 Heart rate higher than 100 beats/min
 Congestive heart failure ,Chronic lung disease ,Cancer

• Cardiac Biomarkers and Imaging
 Elevated troponin I or troponin T
 Elevated BNP or pro-BNP
 Right ventricular hypokinesis on echocardiogram
 Right ventricular enlargement on chest CT
Anticoagulation
Unfractionated heparin (UFH) prevents additional

thrombus formation and permitting endogenous fibrinolytic
mechanisms to lyse clot that has already formed.
• UFH is dosed to achieve a target (aPTT) that is 2–3 times
the upper limit of the laboratory normal. This is usually
equivalent to an aPTT of 60–80 s.
• For UFH, a typical IVbolus is 5000–10,000 units followed by
a continuous infusion of 1000–1500 units/h.
• The most popular nomogram utilizes an initial bolus of 80
units/kg, followed by an initial infusion rate of 18 units/kg
per hour.

• The major advantage of UFH is that it has a short half-life.

• The major disadvantage of UFH is that achieving the target
aPTT can be difficult and may require repeated blood
sampling and heparin dose adjustment every 4–6 h.
Raschke Nomogram

 Variable
Action

 Initial IV heparin bolus 80 U/kg bolus,
then 18 U/kg/hr

 aPTT <35 seconds (<1.2 × control) 80 U/kg bolus,
then increase by

4 U/kg/hr
aPTT 35 - 45 seconds (1.2 -1.5 c) 40 U/kg bolus, then
by 2 U/kg/hr

 aPTT 46 - 70 seconds (1.5 to 2.3 c) No change

 aPTT 71 - 90 seconds (2.3 to 3 c ) infusion rate
• Low Molecular Weight Heparins:

 exhibit less binding to plasma proteins and endothelial
cells and consequently have greater bioavailability, a more
predictable dose response, and a longer half-life than UFH.

 -No monitoring or dose adjustment is needed unless the
patient is markedly obese or has renal insufficiency.

• Enoxaparin 1 mg/kg twice daily and tinzaparin 175 units/kg
once daily have received FDA approval for treatment of
patients who present with DVT.

• The weight-adjusted doses must be adjusted downward in
renal insufficiency because the kidneys excrete LMWH

• Fondaparinux:
 -Fondaparinux, an anti-Xa pentasaccharide, is
administered by once-daily subcutaneous injection and has
been approved by the FDA to treat DVT and PE.

 -No laboratory monitoring is required.

 -Patients weighing <50 kg receive 5 mg,
 50–100 kg receive 7.5 mg, and
 >100 kg receive 10 mg.

 -The dose must be adjusted downward for patients with
renal dysfunction because the drug is excreted by the
kidneys.
Warfarin
• This vitamin K antagonist prevents carboxylation activation
of coagulation factors II, VII, IX, and X.

• The full effect of warfarin requires at least 5 days.

• If warfarin is initiated as monotherapy a paradoxical
exacerbation of hypercoagulability can increase the
likelihood of thrombosis rather than prevent it.

• Overlapping UFH, LMWH, or fondaparinux with warfarin for
at least 5 days can counteract the early procoagulant
effect of unopposed warfarin.

Warfarin

• Dosing
 - In an average-sized adult, warfarin is usually initiated in
a dose of 5 mg.

 -Doses of 7.5 or 10 mg can be used in obese or large-
framed young
 patients who are
otherwise healthy.

 - Patients who are malnourished or who have received
prolonged courses of antibiotics are probably deficient in
vitamin K and should receive smaller initial doses of
warfarin, such as 2.5 mg.

 -The prothrombin time is standardized with the INR.

 -The target INR is usually 2.5, with a range of 2.0–3.0
Optimal Duration of Anticoagulation

• Clinical Setting
Recommendation
 1ST provoked PE/proximal leg DVT 6
mo

 First provoked upper extremity DVT 3
mo
 or isolated calf DVT

 Second provoked VTE
12 mo
 or
indefinite duration

 Third VTE
Indefinite duration

Inferior Vena Caval Filters

• The indications for insertion of an IVC filter are
 (1) active bleeding that precludes anticoagulation,
and
 (2) recurrent venous thrombosis despite intensive
anticoagulation

• Prevention of recurrent PE in patients with Rt. heart failure
who are not candidates for fibrinolysis or prophylaxis of
extremely high-risk patients are "softer" indications for
filter placement.

• The filter itself may fail by permitting the passage of small
to medium-sized clots.
• Large thrombi may embolize to the pulmonary arteries via
collateral veins that develop.
• A more common complication is caval thrombosis with
marked bilateral leg swelling
Inferior Vena Caval Filters

• Retrievable filters can now be placed for patients with
 -an anticipated temporary bleeding disorder or
 -for patients at temporary high risk of PE

• The filters can be retrieved up to several months following
insertion, unless thrombus forms and is trapped within
the filter.

• The retrievable filter becomes permanent if it remains in
place or if, for technical reasons such as rapid
endothelialization, it cannot be removed
Maintaining Adequate Circulation

• For patients with massive PE and hypotension, the most
common initial approach is administration of 500–1,000
ml of normal saline.

• However, fluids should be used with extreme caution.

• Excessive fluid administration exacerbates RV wall stress,
causes more profound RV ischemia, and worsens LV
compliance and filling by causing further IVS shift
toward the LV.

• Dopamine and dobutamine are first-line inotropic agents
for treatment of PE-related shock.
Fibrinolysis

• Thrombolysis usually
 (1) dissolves much of the obstructing pulmonary arterial
thrombus
 (2) prevents the continued release of serotonin and other
neurohumoral
 factors that exacerbate pulmonary hypertension and
 (3) dissolves much of the source of the thrombus in the
pelvic or
 deep leg veins, thereby decreasing the likelihood of
recurrent PE.

• The preferred fibrinolytic regimen is 100 mg of recombinant
tissue plasminogen activator (tPA) administered as a
continuous peripheral IV infusion over 2 h.

• Patients appear to respond to fibrinolysis for up to 14 days
Fibrinolysis

• Contraindications to fibrinolysis include intracranial disease,
recent surgery, or trauma.

• The overall major bleeding rate is about 10%, including a 1–
3% risk of intracranial hemorrhage.

• Indication for PE fibrinolysis is massive PE.

• For patients with preserved systolic blood pressure and
submassive PE, guidelines recommend individual patient
risk assessment of the thrombotic burden versus
bleeding risk
MANAGEMENT

• Pulmonary Embolectomy

 -The risk of intracranial hemorrhage with fibrinolysis
has prompted
 the renaissance of surgical
embolectomy for acute PE
 - At Brigham and Women's Hospital, 47 patients with
massive PE
 underwent emergency surgery in 53 months, with a
94% survival rate

• Alternative to open surgical embolectomy is catheter
embolectomy
Pulmonary Thrombo endarterectomy
• Chronic thromboembolic pulmonary hypertension is caused
by vascular obstruction at the capillary level, not direct
thromboembolic occlusion

• Patients severely impaired with dyspnea due to chronic
thromboembolic PHTN should be considered for
pulmonary thromboendarterectomy, which, if successful,
can markedly reduce and at times even cure PHTN.

• The two most common complications are

 (1) "pulmonary steal," where blood rushes from
previously perfused
 areas to newly revascularized areas of
the lung; and

Prevention of Postphlebitic Syndrome

• The only therapy to prevent postphlebitic syndrome is daily
use of below-knee 30–40 mmHg vascular compression
stockings.

• They halve the rate of developing postphlebitic syndrome.

• These vascular compression stockings should be prescribed
as soon as DVT
 is diagnosed, and the stockings should be fitted carefully
to maximize
 their benefit.
Prevention of VTE
• REFERENCES:

 Harrison's Internal Medicine ,17th e

 Braunwald’s Heart Disease ,8th e

 Cecil Medicine, 23rd ed.