Pulmonary embolism

Dragoş Bumbăcea, MD, PhD, MPH, FCCP

Department of Pneumology
Elias Emergency University Hospital
Carol Davila University of Medicine and Pharmacy
 Definition
● Obstruction of a pulmonary artery or one of its branches by
material (e.g., thrombus, tumor, air or fat) originating elsewhere in
the body
● Pulmonary embolism due to thrombus = manifestation of Venous
Thromboembolism (include Deep Venous Thrombosis DVT)
● Other types of emboli:
● Air embolism
● Fat embolism
● Pulmonary embolism
● Acute
● Chronic – slowly progressive dyspnoea due to pulmonary hypertension
 Epidemiology
● Incidence:
● 62.1 – 112.3 in 100.000 adults (USA)
● 55.3 – 71.7 in 100.000 insured (Germany)
● Natural history:
● Mortality: 30%
● Morbidity – unknown, estimated to be important!
 Predisposing factors – genetic
● Factor V Leyden
● Prothrombin G20210A
● Antithrombin deficiency
● Protein C deficiency
● Protein S deficiency
● Increased factor VIII
● Increased factors II, IX, XI
● Increased levels of TAFI Probably genetic
● Reduced levels of TFPI
 Predisposing factors – acquired
● Age
● History of thrombosis
● Neoplasm
● Immobilisation
● Major surgery
● Pregnancy & puerperal period & hormonal treatment
● Hospitalisation
● Obesity
● Infection
● Resistance to activated Protein C, non-genetic
● Antiphospholipidic syndrome
 Physiopathology
● Source:
● Lower limbs deep venous system
– Thrombi in proximal veins (illiac, femoral, popliteal)
– Thrombi in calf veins – usually spontaneous resolution, but 20-30%
extend in proximal veins
● renal, pelvic, upper limb veins, right heart
● Embolus
● Large pulmonary arteries (bifurcation → lobar arteries) –
haemodynamic alteration
● Distal pulmonary arteries – pleuritic chest pain, pulmonary
infarctus
 Pathophysiology
● Gas exchange alteration
● mechanical obstruction + ventilation/perfusion mismatch
● inflammatory mediators with: surfactant dysfunction,
atelectasis, intrapulmonary shunt
● Arterial hypotension – due to decrease in cardiac
output, secondary to increase in pulmonary
vascular resistance:
● Obstruction by thrombus
● Vasoconstriction (inflammatory mediators, hypoxia)
 Symptoms
● Exercise / rest dyspnoea – acute onset (seconds –
minutes)
● Pleuritic chest pain
● Cough
● Wheezing
● Orthopnea
● Calf or thigh pain
● Calf or thigh oedema
 Physical signs
●
Pulmonary embolism
● Tachypnea
● Tachycardia
● Rarely systemic hypotension
● Rales
● Decreased breath sounds
● Increased pulmonic component of the second heart sound
● Jugular vein distension
●
Deep venous thrombosis
● Oedema
● Erythema
● Pain
● Palpable vein cord in the calf or thigh
 Differential diagnosis
(Great imitator)
● Pneumonia
●
Asthma (wheezing)
●
Chronic obstructive pulmonary disease
● Congestive heart failure
● Pericarditis
●
Pleurisy
●
Rib fracture
●
Pneumothorax
● Acute coronary syndrome
●
Anxiety
 Initial tests
● Chest X-ray
● ECG
● Arterial blood gases
 PE signs on chest X-ray
● Atelectasis
●
Pulmonary infiltrates
●
Raised diaphragm
● Unilateral hilum enlargement
● Mediastinal enlargement
●
Cardiomegaly (Chronic PE)
●
Localized oligemia (Westermak's sign)
●
Prominent central pulmonary artery
● Pleural-based opacity (Hampton's bump)
●
Pulmonary oedema
Westermark's sign
Linear atelectasis + pleural fluid
 PE signs on ECG
● Rhythm disturbances: sinus tachycardia, atrial fibrillation,
atrial flutter, etc
● Left or right QRS axis deviation
● Right bundle branch block
● P pulmonale
● ST/T abnormalities
● S1Q3T3
● Q wave in DIII and aVF
● Large S wave in DI and aVL
 Arterial blood gases
● Hypoxaemia
● Hypocapnia and respiratory alkalosis
● Increased O2 alveolar-arterial gradient
● No utility:
● 10-15% have normal PaO2 and PaCO2
● Do not differentiate from other causes
● Massive PE (hypotension) – hypercapnia and mixed
respiratory and metabolic (lactic) acidosis
 Diagnostic tests
● Plasma D-dimer test
● Compression venous ultrasound
● CT pulmonary angiography
● Pulmonary scintigraphy
● Pulmonary angiography
● Contrast phlebography
 Plasma D-dimer
● > 500 ng/mL = abnormal
● High sensitivity → High negative predictive value
● Most PE patients have abnormal D-dimer levels
● A normal D-dimer level excludes PE in patients with low or moderate pre-test
probability
● Moderate specificity → Moderate positive predictive value
● Many patients without PE have abnormal results (mostly cancer or post-
surgical period)
● An abnormal D-dimer result is not sufficient to confirm PE
● D-dimer test is used to EXCLUDE PE in patients with low-to-
moderate pre-test probability
● Cheap, simple – first line test in these patients
 Venous ultrasound
● Acute DVT criteria:
● Lack of vein compressibility
● Vein does not “wink” on cross-section compression
● Failure to appose walls of veins due to passive distention
● Has replaced contrast phlebography
● Positive result (= DVT) is considered sufficient as
PE treatment is similar to DVT's!!
● Negative result DO NOT EXCLUDE PE!!!
 CT pulmonary angiography
● Main imaging diagnostic method for PE
● Multidetector CT (Spiral CT) – excellent resolution
down to sub-segmental emboli
● Excellent imaging for right and left ventricles –
severity evaluation
● May be continued down to knee level – pelvic and
lower limb DVT diagnosis
● Differential diagnosis: pneumonia, emphysema,
fibrosis, cancer
Saddle embolus
Right pulmonary artery
Right and left pulmonary arteries
Left lower lobe artery
Right lower lobe artery
Subsegmental arteries
 Diagnsotic value of CT pulmonary
angiography
● Positive – confirms PE
● Negative:
● Exclude PE in patients with low-to-moderate PE
probability
● Cannot exclude PE in patients with high PE
probability
 Pulmonary scintigraphy
● Lung perfusion scintigraphy: radionuclide-labeled albumin injected
intravenously
● Perfusion defect (=absence of perfusion) – due to PE or other causes
● Lung ventilation scintigraphy: radionuclide-labeled xenon or krypton
● Ventilation defect (= absence of ventilation) – due to other causes, NOT PE
● Normal scintigraphy – excludes PE
● High-probability scintigraphy (≥ 2 perfusion segmental defects with
normal ventilation) – confirms PE
● Low-to-moderate probability (most patients) – non-diagnostic test
 V/Q scintigraphy in PE

Normal ventilation
Several perfusion deficits, including whole left lung
 Algorithm (example)
PE suspect

Clinical probability
evaluation
(modified Wells)

Low-to-moderate probability High probability

D-dimer
AngioPulmCT

normal abnormal
Confirmation Unconclusive Alternate dg

Excludes PE
PE treatment ?angiography? Treatment
 Exclude PE?
● Low clinical probability
+
● Presence of ALL of the following (PE rule-out criteria PERC)
● Age less than 50 years
● Heart rate less than 100 bpm
● Peripheral oxygen saturation ≥ 95%
● No haemoptysis
● No oestrogen treatment
● No history of DVT or PE
● No uniilateral calf oedema
● No surgical intervention or trauma that required hospitalisation in the last 4
weeks
 Severity evaluation
● Hypotension (systolic BP < 90 mmHg, diastolic BP < 60 mmHg)
● = massive PE, high death risk (10-15%)
● Right ventricular dysfunction (intermediate risk 3-11%)
● RV dilation, hypokinesia or pressure overload on cardiac ultrasound
● RV dilation on angioCT
● Increased BNP or NT-proBNP
● Increased pressure in the right heart at right heart catheterism
● Myocardial injury (intermediate risk 3-11%)
● Increased troponin T or I
● Low risk PE (< 1%) in the absence of all above criteria
 Attitude
● High risk (massive PE)
● Thrombolysis
● Embolectomy
● Intermediate risk (sub-massive)
● Hospitalization
● Anticoagulant
● Low risk
● Home treatment
● Anticoagulant
 Treatment
● Haemodynamic and respiratory support
● In patients with hypotension
● Fluids
● Vasopressor treatment
● Rarely ventilation
● Thrombolysis
● Anticoagulant
 Thrombolysis
● rtPA
● 100 mg in 2 h
or
● 0.6 mg/kg in 15 min (maximal dose 50 mg)
● Indication: massive PE (hypotension)
● Contraindications (absolute):
● Haemorrhagic or undefined stroke at any time
● Ischaemic stroke in the last 6 months
● Neoplasm or other central nervous system disease
● Trauma / Surgery / Recent head trauma (last 3 weeks)
● Gastrointestinal haemorrhage in the last months
● Known haemorrhage at any site
 Anticoagulant treatment
●
All patients (including those on thrombolysis)
●
Rapid (life-saving)
●
Initial – heparin:
● Unfractionated heparin: dose adjusted according to aPTT
● Low molecular weight heparin
– Enoxaparin 1mg/kg x 2/day
– Tinzaparin 175 units/kg once a day
● Fondaparinux
●
Adverse effects:
● Haemorrhage (antidote: protamine sulphate)
● Heparin-induced thrombocytopenia
 Anticoagulant treatment
● Anti-vitamin K (AVK)
● Acenocumarol (Ro)
● Warfarin (US, other)
● Target: INR 2.0-3.0
● Initial procoagulant effect – minimum 5 days overlap
with heparin
● Adverse effects – haemorrhage (treated with fresh
plasma)
● Contraindicated in pregnancy (only heparin)
 Duration of anticoagulation
● Recurrence risk: ● Haemorrhage risk:
● age >65 years
● Low in: first PE
episode + reversible
● previous haemorrhage
risk factor (surgery, ● thrombocytopenia, antiagregant
treatment, poor control of
trauma) coagulation
● High in: first PE ● recent surgery
episode + absent or ● frequent falls
non-reversible (cancer) ● reduced functional capacity
risk factor ● history of stroke
● High in recurrent PE ● diabetes, anaemia, cancer, renal
failure, liver failure, alcohol
abuse
 Duration of anticoagulation
● First PE episode
● Provoked, reversible risk factor: 3 months
● Unprovoked or Provoked with non-reversible risk
factor:
– Low haemorrhage risk: indefinitely (periodic re-
evaluation)
– High haemorrhage risk: 3 months
● Recurrent PE – similar to unprovoked PE, but
with a larger benefit of indefinite anticoagulation
 Inferior vena cava filter
● Indications:
● Active haemorrhage (contraindication of
anticoagulation)
● Recurrent deep venous thrombosis despite correct
anticoagulation
● Technique: introduction through common
femoral vein catheterism
● Risk of filter thrombosis!
 DVT (and PE) prevention
● Indications:
● Surgery
● Medical diseases (heart failure, stroke, etc)
● Long airflights in high-risk patients
● Methods:
● Pharmacological
– Mini-dose of unfractionated heparin (5000 UI s.c. X 2-3/day)
– LMWH: enoxaparin 40 mg/day s.c.
● Mechanical:
– Elastic stockings
– Pneumatic compression systems
 Conclusions
● PE is difficult to diagnose!
● Diagnostic algorithm is based on “rule-out” tests
(D-dimer) and “rule-in” tests (angioCT)
● Anticoagulation is the central therapeutic
element
● Thrombolysis is indicated in life-threatening PE
● DVT prevention is mandatory in the presence of
surgical or medical risk factors