This document discusses pulmonary embolism (PE), including its epidemiology, disease burden, risk factors, pathophysiology, signs and symptoms, diagnostic evaluation, and treatment approaches. It notes that PE has an annual incidence of 100-200 per 100,000 people. Diagnostic evaluations discussed include assessment of clinical probability, D-dimer testing, CT pulmonary angiography, lung scintigraphy, and echocardiography. Treatment of acute PE involves hemodynamic support, anticoagulation with unfractionated heparin, low molecular weight heparin or fondaparinux, and potentially thrombolysis for high-risk cases.

1. Pulmonary Embolism
Dr. Uttam Laudari
JR-II
Department of Surgery

2. Epidemiology
• Venous thromboembolism (VTE) encompasses deep vein thrombosis
(DVT) and pulmonary embolism (PE).
• It is the third most frequent cardiovascular disease with an overall annual
incidence of 100–200 per 100 000 inhabitants.1
• VTE may be lethal in the acute phase or lead to chronic disease and
disability, but it is also often preventable.
Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler
Thromb Vasc Biol 2008;28(3):370–372.

3. Disease burden
• As estimated on the basis of an epidemiological model, over 317 000
deaths were related to VTE in six countries of the European Union (with a
total population of 454.4 million) in 2004.
34%
59%
7%
percentage
sudden fatal
death
deaths from
undiagnosed
PE
deaths after
diagnosed
Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, Greer IA, Heit JA, Hutchinson JL, Kakkar AK,
Mottier D, Oger E, Samama MM, Spannagl M. Venous thromboembolism (VTE) in Europe. The number of VTE events
and associated morbidity and mortality. Thromb Haemost 2007;98(4):756–764.

5. Predisposition
Patient related
PERMANENT RISK
FACTORS
UNPROVOKED
Settings related
TEMPORARY RISK
FACTORS
PROVOKED
Pulmonary Embolism

6. Temporary or Reversible risk factor
surgery, trauma, immobilization,
pregnancy,
oral contraceptive use or hormone
replacement therapy)
within the last 6 weeks to 3 months
before diagnosis
PROVOKED
UNPROVOKED In the absence of above

7. • Major trauma, surgery, lower limb fractures
and joint replacements ,and spinal cord injury,
are strong provoking factors for VTE.
• Cancer
– Haematological malignancies, lung cancer,
gastrointestinal cancer, pancreatic cancer
and brain cancer carry the highest risk

8. • OCPS
• Pregnancy
– risk is highest in the third trimester of pregnancy and over the 6 weeks of the postpartum
period, being up to 60 times higher compared with the risk in non-pregnant women
• post-menopausal women who receive hormone replacement therapy
• Infection
• Blood transfusion and erythropoiesis-stimulating agents
• Children's- chronic medical conditions, Central lines
• cigarette smoking, obesity, hypercholesterolaemia, hypertension and diabetes
mellitus
• Myocardial infarction and heart failure

9. Pathophysiology
Embolization
• When venous thrombi are dislodged from their site of formation,
• they embolize to the pulmonary arterial circulation
• or paradoxically, to the arterial circulation through a patent foramen ovale
or atrial septal defect

10. • About one-half of patients with pelvic vein thrombosis or proximal leg DVT
develop PE, which is often asymptomatic.
• Isolated calf vein thrombi pose a much lower risk of PE but
are the most common source of paradoxical embolism.
• These tiny thrombi can traverse a patent foramen ovale or
atrial septal defect, unlike larger, more proximal leg thrombi.

11. Physiology
• The most common gas exchange abnormalities are hypoxemia
(decreased arterial PO2) and an increased alveolar-arterial O2
tension gradient, which represents the inefficiency of O2
transfer across the lungs.

12. • 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.

13. Increased pulmonary
vascular resistance
pulmonary artery
obstruction
+
Serotonin ( produced by
platelets)
Impaired gaseous
exchange
•Increased dead space
•Hypoxemia – alveolar
hypoventillation
relative to perfusion in
other lung
•Right to left shunt
Increased airway
resistance
•constriction of
airways distal to the
bronchi

14. Decreased pulmonary compliance due to lung edema, lung
hemorrhage, or loss of surfactant
Alveolar hyperventilation due to reflex stimulation of irritant
receptors.

15. Right ventricular dysfunction
• pulmonary vascular resistance
increases
• Increased RV wall tension – RV
dysfunction
• interventricular septum bulges into
and compresses an intrinsically
normal left ventricle.
• Diastolic LV impairment due to
septal displacement,
• reduced LV distensibility and
impaired LV filling during diastole.

16. Right ventricular dysfunction
• Increased RV wall tension also compresses
the right coronary artery
diminished subendocardial perfusion
limits myocardial oxygen supply
myocardial ischemia and RV infarction

17. • LV Underfilling
– fall in left-ventricular
cardiac output and
systemic arterial pressure
– provoking myocardial
ischemia due to
compromised coronary
artery perfusion.
– Eventually, circulatory
collapse and death may
ensue

19. • Dyspnoea
– may be acute and severe in central PE
– in small peripheral PE, it is often mild and may be transient.
– In patients with pre-existing heart failure or pulmonary disease,
worsening dyspnoea may be the only symptom indicative of PE
• Chest pain
– caused by pleural irritation due to distal emboli causing pulmonary
infarction
– In central PE, chest pain may have a typical angina character, possibly
reflecting RV ischaemia and requiring differential diagnosis with
acute coronary syndrome (ACS) or aortic dissection

20. • ABG-
– hypoxaemia
– 40% of the patients have normal arterial oxygen saturation
– 20% a normal alveolar-arterial oxygen gradient.
– Hypocapnia is also often present.
• The chest X-ray is frequently abnormal
– its findings are usually non-specific in PE,
– it is useful for excluding other causes of dyspnoea or chest pain.
– focal oligemia (Westermark's sign),
– a peripheral wedged-shaped density above the diaphragm (Hampton's
hump)
– and an enlarged right descending pulmonary artery (Palla's sign).

21. Electrocardiographic
• changes indicative of RV strain,
– such as inversion of T waves in leads V1–V4,
– a QR pattern in V1,
– S1Q3T3 pattern,
– incomplete or complete right bundle-branch block
• These electrocardiographic changes are usually found in more
severe cases of PE
• milder cases, the only anomaly may be sinus tachycardia, present in
40% of patients.
• Finally, atrial arrhythmias, most frequently atrial fibrillation, may be
associated with acute PE

23. Assessment of clinical probability
Wells criteria
Previous PE or
DVT
1.5
Hear rate
>100bpm
1.5
Surgery or
immobilsation
in past 4 weeks
1.5
hemoptysis 1
Active cancer 1
Clinical signs of
DVT
3
Alternative
diagnosis less
likely than PE
3
Clinical
probability
score- three
level
PE
probablity
Low 0-1 10%
Intermediate 2-6 30%
high >7 65%

24. Clinical
probability
score- three
level
Low 0-3 (10%)
Intermediate 4-10(30%)
high >11(65%)

25. D- dimer
fibrin is also produced in a
wide variety of conditions
such as- cancer,
inflammation, bleeding,
trauma, surgery and
necrosis.
sensitivity of the d-dimer
is >80% for DVT (including
isolated calf DVT) and
>95% for PE.

26. D- dimer
• The d-dimer is less sensitive for DVT than for PE because the
DVT thrombus size is smaller.
• The d-dimer is a useful "rule out" test.
• More than 95% of patients with a normal (<500 ng/mL) d-
dimer do not have PE.

27. • The specificity of D-dimer in suspected PE decreases steadily with age, to
almost 10% in patients >80 years
• Recent evidence suggests using age-adjusted cut-offs to improve the
performance of D-dimer testing in the elderly
• In a recent meta-analysis, age-adjusted cut-off values (age x 10 mg/L
above 50 years) allowed increasing specificity from 34–46% while
retaining a sensitivity above 97%

28. CT Pulmonary angiography
Sensitivity-83%
specificity-96%
Also obtains
excellent images of
the RV and LV and
can be used for risk
stratification along
with its use as a
diagnostic tool

29. CT Pulmonary angiography
• It allows adequate visualization of the pulmonary arteries down to at least the
segmental level
• RV enlargement on chest CT indicates an increased likelihood of death within the
next 30 days compared with PE patients who have normal RV size on chest CT.
• imaging is continued below the chest to the knee pelvic and proximal leg DVT
also can be diagnosed by CT scanning.
• Rules out other
– pneumonia, emphysema, pulmonary fibrosis, pulmonary mass, and aortic pathology.

30. Lung scintigraphy
• second-line diagnostic test for PE
• used mostly for patients who cannot tolerate intravenous contrast
• Small particulate aggregates of albumin labeled with a gamma-
emitting radionuclide are injected intravenously and are trapped in
the pulmonary capillary bed
• perfusion scan defect indicates absent or decreased blood flow,
possibly due to PE.
• Ventilation scans, obtained with a radiolabeled inhaled gas such as
xenon or krypton, improve the specificity of the perfusion scan.

31. Lung scintigraphy
A high-probability scan for PE is defined as
one that indicates two or more segmental
perfusion defects in the presence of
normal ventilation

32. Lung scintigraphy
• Being a radiation- and contrast medium-sparing procedure, the V/Q scan
may preferentially be applied in outpatients with low clinical probability
and a normal chest X-ray,
– in young (particularly female) patients
– pregnancy
– history of contrast medium-induced anaphylaxis and strong allergic history,
– severe renal failure,
– myeloma and paraproteinaemia

33. Magnetic Resonance (MR)
• suspected VTE patients with renal insufficiency or contrast
dye allergy.
• may detect large proximal PE but is not reliable for smaller
segmental and subsegmental PE.

34. Echocardiography
• useful diagnostic tool for detecting conditions that may mimic
PE, such as acute myocardial infarction, pericardial
tamponade, and aortic dissection
• The best-known indirect sign of PE on transthoracic
echocardiography is McConnell's sign: hypokinesis of the RV
free wall with normal motion of the RV apex

35. Pulmonary angiography
• technically unsatisfactory chest CTs
• interventional procedure such as catheter-directed
thrombolysis or embolectomy is planned.
• 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, and tortuous, tapering
peripheral vessels.

36. diagnostic algorithm for patients with suspected high-risk PE, i.e.
presenting with shock or hypotension

37. Proposed diagnostic algorithm for patients with
suspected not high-risk pulmonary embolism

38. Treatment in Acute phase
• Hemodynamic and respiratory support
• Acute RV failure with resulting low systemic output is the
leading cause of death in patients with high-risk PE.
• Therefore, supportive treatment is vital in patients with PE and
RV failure

39. • Fluid
– aggressive volume expansion is of no benefit
– worsen RV function by causing mechanical overstretch, or
by reflex mechanisms that depress contractility
– modest (500 mL) fluid challenge may help to increase
cardiac index in patients with PE, low cardiac index, and
normal BP

40. Vasopressors
• often necessary, in parallel with (or while waiting for) pharmacological,
surgical, or interventional reperfusion treatment.
• Norepinephrine
– improve RV function via a direct positive inotropic effect
– improves RV coronary perfusion by peripheral vascular alpha-receptor
stimulation and the increase in systemic BP
– Its use should probably be limited to hypotensive patient

41. • Epinephrine combines the beneficial properties of
norepinephrine and dobutamine, without the systemic
vasodilatory effects of the latter.
• It may therefore exert beneficial effects in patients with PE and
shock.

42. Vasodilators
– decrease pulmonary arterial pressure and pulmonary vascular
resistance,
– but the main concern is the lack of specificity of these drugs for the
pulmonary vasculature after systemic (intravenous) administration
– Inhalation of nitric oxide may improve the haemodynamic status and
gas exchange of patients with PE

43. Respiratory support
• Hypoxaemia and hypocapnia are frequently encountered in
patients with PE, but they are of moderate severity in most
cases.
– oxygen
– mechanical ventilation

44. • Mechanical ventilation
– Careful to limit its adverse haemodynamic effects
– the positive intrathoracic pressuremay reduce venous
return and worsen RV failure in patients with massive PE
– Low tidal volumes (approximately 6 mL/kg lean body
weight) and end-inspiratory plateau pressure 30 cm H2O.

45. Anticoagulation
• In patients with acute PE, anticoagulation is recommended, with the
objective of preventing both early death and recurrent symptomatic or fatal
VTE
• The standard duration of anticoagulation should cover at least 3 months
• acute-phase treatment consists of administering parenteral anticoagulation
[unfractionated heparin (UFH), LMWH or fondaparinux] over the first 5–
10 days.
• Parenteral heparin should overlap with the initiation of a vitamin K
antagonist (VKA)

46. UFH
• Binds to antithombin III
• inhibits factor IIa ( Thrombin) and facto Xa and also F
IXa,XIa and XIIA of coagulation cascade
• Dose-
– IV bolus- 80u/kg
– Followed by continious IV drip at 18units/kg/hr
– T1/2- 45-90min (dose dependent)
– Monitoring- aPTT 6hourly
– aPTT goal- 1.5 to 2 times the control value

47. Complication of UFH
1.Hemorrahage
– Fatal, intracranial hemorrhage, retroperitoneal or
requiring >2 unit of packed red cell is aprox 5 % in
hospitalized patient
• Management
– Discontinue UFH
– Protamine sulphate
• 1mg protamine neutralizes 90-115 unit of heparin
• Dose not to exceed 50mg IV over any 10 min

48. Complication of UFH
2. HIT
• Results due to heparin associated antiplatelets antibody
complex
• Repeated heparin exposure( vascular Sx- 21%)
• Occurs m/c in 2nd week of therapy
• Platelet counts to be monitored periodically
• Dx- exposure to Heparin + platelets <100,000 and/ or
decline in 50% of platelet following exposure

49. Complication of UFH
3. Heparin induced osteopenia
impairment of bone formation and enhancement of
bone resorption by heparin

50. LMWH(enoxaparin)
• Derived from polymerization of porcine UFH
• Act more on F Xa
• Increased bioavailability
• 2-4 times longer half life
• Can be administered S.C without lab monitoring
• Img/kg 12hrly and 1.5mg/kg OD
• Partially reversible by protamine (60%)
• Patient requiring monitoring
– Severe renal impairment, pediatrics,pregnants, wt>120kg
• HIT <2%
• Established HIT- not be used
• Outpatient treatment
• Reduce hospital stay

51. Fondaparinux
• Synthetic petasaccharide
• Activated antithrombin and Xa inhibiion
• Recurrent VTE- 3.8-5%
• Major bleeding- 2-2.6%
• Administered – SC once daily dose
• Half life 17 hour

52. Direct thrombin inhibitors
• Hirudin,argatroban and bivalirudin
• Binds thrombin and inhibiting conversion of fribrinogen to
fibrin and fribrin induced thrombocytopenia
• Used for high suspicion/confirmed HIT or with history of
HIT or HAAb positive cases
• Requires aPTT adjustment

53. Vitamin K antagonist
• Main stay of long term antithrombotic therapy
• Warfarin and other coumarin derivatives
• Inhibits gamma carboxyaltion of Vit K dependent factors and protein C and S
• Requires several days to achieve full effect ( 4-5 days)
• Monitored by INR
• INR= (patient PT/lab normal PT)*ISI
• ISI- international senstivity index- strength of thromboplastin that is added to
activate the extrinsic coagualtion pathway

54. warfarin
• Therapeutic range- 2-3
• To be started on same day of starting parenteral
anticoagualation ( except with concomitant thrombolysis and
venous thrombectomy)
• Usual starting dose 50-10mg
• Smaller dose for older, malnourished, liver disease and CHF
• Variability of response
– Depends upon Liver funtion, diet, age and medicaitons used

55. Fibrinolysis
The only FDA-approved indication for PE
fibrinolysis is massive PE

56. Fibrinolysis
• rapidly reverses right heart failure and may result in a lower
rate of death and recurrent PE
– dissolving much of the anatomically obstructing pulmonary arterial
thrombus
– preventing the continued release of serotonin and other neurohumoral
factors that exacerbate pulmonary hypertension
– lysing much of the source of the thrombus in the pelvic or deep leg
veins, thereby decreasing the likelihood of recurrent PE.

57. • preferred fibrinolytic regimen
– 100 mg of recombinant tissue plasminogen activator (tPA)
administered as a continuous peripheral intravenous infusion over 2
hours.
– Patients appear to respond to fibrinolysis for up to 14 days after the PE
has occurred

58. Contraindication of Fibrinolysis
• intracranial disease
• recent surgery and trauma
• The overall major bleeding rate is about 10%, including a 1–
3% risk of intracranial hemorrhage.

59. Surgical Embolectomy
•high-risk PE
•selected patients with
intermediate-high-risk PE,
particularly
if thrombolysis is
contraindicated or has
failed.

60. Percutaneous catheter-directed
treatment
•Administer lytic agent alone
•Pharmacomechanical clot lysis

61. Venous filters
1. acute PE with absolute contraindications
to anticoagulant drugs
2. patients with objectively confirmed
recurrent PE despite adequate
anticoagulation treatment

62. Recommendations for duration of anticoagulation after
pulmonary embolism
PE secondary to transient risk factor 3 months
Unprovoked PE At least 3 months
Class IB
second episode of
unprovoked PE
Indefinite duration
Class IA
PE with Cancer LMWH should be considered for the
first 3–
6 months. IIA
Extended anticoagulation (beyond the
first 3–6 months) should be
considered for an indefinite
period or until the cancer is
Cured . IIC
2014 ESC Guidelines on the diagnosis and management of acute
pulmonary embolism

63. In patients who receive extended anticoagulation, the risk–benefit ratio
of continuing such treatment should be reassessed at regular intervals. IC
In patients who refuse to take or are unable to tolerate any form of oral
anticoagulants, aspirin may be considered for extended secondary VTE
prophylaxis. IIB
2014 ESC Guidelines on the diagnosis and management of acute
pulmonary embolism

65. Summary