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
 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 lt PA thrombus anticoagulation
or “high clot burden”
Submassive PE Hemodynamically stablebut Addition of thrombolysis,
mod. or sev.RVdysfunction embolectomy or filter
or enlargement remains controversial

Small to mod.PE Normal hemodynamics and Anticoagulation

normal RV size and function
 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.

-Intravenous drug abusers sometimes self-inject hair, talc, and cotton

that contaminate the drug they have acquired
 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 axis
-AF or Atrial flutter
 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.

• Transesophageal echo 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 oligemia or 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 by 2 U/kg/hr

aPTT >90 seconds (>3 c) Hold infusion 1 hr, then decrease

infusion rate by 3 U/kg/hr
• 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

Cancer 6 mo
or indefinite duration

Unprovoked VTE Consider 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 after the PE

has occurred.
 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

(2) reperfusion pulmonary edema

 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.