Pulmonary embolism (PE)
is a very critical disease: if not timely known and treated could be lethal
in about 10%. Main problems are diagnostic because PE does not present specific
signs or symptoms and often it is not easy to identify the presence of deep
venous thrombosis (DVT) which represents the cause of PE in more of 80% (1).
PE is the third cause of death after stroke and myocardial infarction (6).
It represents 1% of all in-of-hospital death, with a presumed incidence of
0.1% of population (2). The incidence doubles every decade: it is rare before
40’s (3), it is more frequent after 65’s and in male. Its incidence is just
lower than stroke.
English studies demonstrated that 1% of the in-of-hospital population is affected
by DVT (4). In United States the incidence of DVT is 750.00 cases per annum
with 200.000 – 300.000 hospital admissions, while in Italy every year 60.000
new cases are described with an early mortality of 30% within 1 hours from
the beginning of the symptoms.
The increase of the mean age of the population and the higher number of patients
with a longer survival during neoplastic, cardiac and pulmonary diseases could
cause in the future an important increase of PE for the healthcare system.
Therefore the exact knowledge of the suggestive symptoms of the PE is of primary
importance.
CLINICAL PRESENTATION
PE is a potentially fatal condition, with an irregular clinical presentation
and no signs and symptoms that could be considered specific. Therefore clinical
evaluation of patient with a suspected PE shall be careful monitored because
is the main element of the diagnostic iter.
Simptomatology is widely irregular and reflects the importance of vascular
pledge. In non-massive model, the most frequent symptoms are the dyspnoea,
chest pain, while the syncope is more frequent in massive models(5). Sometimes
patient can report pleuric pain, due to pulmonary infarction or distal embolism.
An unclear tachycardia or night dry cough are the only elements useful for
the diagnosis pulmonary microembolism. Improvised and severe dyspnoea is due
to the involvement of large pulmonary vessels, while chest pain, like the
angina one, is due to the ischaemia left ventricle and is coupled with a severe
haemodynamic failure.
Syncope or severe hypotension are expression of massive PE coupled with signs
and symptoms of hypoperfusion like, cyanosis an oliguria.
DIAGNOSIS
PE is a syndrome of very difficult diagnosis: it is very important to suspect
the disease, to make diagnosis, but as signs and symptoms are very unspecific
(7- 9), objective test are necessary.
Electrocardiogram –
Its role is to exclude other cardiac diagnosis such as: the pericarditis,
the myocardial infarction.
The electrocardiogram can show a right systolic and/or diastolic pledge (high
R in V1, recent right brunch block) S1 – Q3, negative T in the precordial
(ischaemia due to the compression of coronary arteries). It is useful in the
forms with right ventricular dysfunction.
Blood Gas Analysis –
Hypoxemia is very frequent during PE, but about 20% of patients (young people)
can show a normal oxygen partial pressure even during the PE.
As hypocapnia is almost always present, it has been supposed that an increased
oxygen alveolar-arterial difference could be a more diagnostic for PE. The
results of recent studies does not confirm this hypothesis because 15 –20
% of patients have a normal oxygen alveolar-arterial difference (10). Chest
X-ray – reason of utilise -exclusion of pneumothorax, pneumonia, pulmonary
oedema, cancer, etc. -can be suggestive of PE, when present pulmonary infarction
or haemorrhage (parenchimal opacity or semicircular atelectasia with the basis
on the pleura surface, 51%) (20). In pulmonary haemorrhage the opacity vanishes
in one week, while in pulmonary infarction in 8 – 12 weeks.
Other typical findings of PE are pleura collection (38% typically little,
interesting only the costo-frenic angle), subsegmentary atelectasia, pulmonary
infiltrate; rarely oligoemia is present (Westermark’s sign. 1l %), regional
oligoemia with pulmonary artery omolateral enlargement (Fleischer’s sign)
(Figure 1).
Figura 1: oligoemia
al campo superiore dx (segno di Westermark) e opacità basale a sx (segno di
Hampton)
Figure 1: oligoemia of right superior space (Westermark’s sign) e and left
basal opacity (segno di Hampton)
Figura 2: Angiografia
polmone sx: Difetti di riempimento dei rami delle arterie del lobo inferiore
sx (freccette)
Figure 2: Pulmonary angiography: Filling defects of pulmonary arteries of
left inferior lobe
-For a right interpretation
of pulmonary perfusion scintigraphy in patient affected by a non embolic perfusion
defect as COPD, emphysema, pulmonary fibrosis, surgical operation, infection,
recent radiotherapy (11).
Echocardiogram
Echocardiogram is a non invasive test, available in almost all medical centre
that can be very useful in the diagnosis of PE. A dilatation and hypocinesia
of right ventricle free wall, an increased rate RV/LF(due to the bulging of
the septum into the left ventricle), the dilatation of proximal pulmonary
arteries, a tricuspid insufficiency and finally a dilatation of inferior cava
vein, unmodified by respiratory excursions, can address for a diagnosis of
massive PE (12). The entity of right ventricle failure is the prognostic factor
with a higher mortality in the shortest time.
No echo finding is related to a high sensibility and only the direct view
of the pulmonary embolus, with the transoesophagus echocardiogram, allow to
perform diagnosis of PE.
A normal echocardiogram test is able to exclude a PE of relevant haemodynamic
involvement, but is not able to exclude mild form of PE. For all the intermediary
forms (that represent the greatest part of all PE) the role of echocardiogram
shall be validate with prospective studies, in order to identify patients
with PE who can be treated with thrombolytic therapy even when systemic hypotension
and shock are absent (13) .
D-Dimer Dosing
The D-Dimer (DD) is a fibrin degrade product. It is the expression of the
thrombin activation and of fibrinolysis. It is measured with quantitative
methods (ELISA) or semiquantitative (latex and similar). While quantitative
test takes 5- 6 hours to present the results, semiqantitative tests present
the results within 20 – 30 minutes. All the methods to test the DD have been
evaluated in several published studies. DD has a negative predictive value
of 98% with a specificity of 35%, due to the fact that coagulation can be
activated by several pathologic condition like cancer, infection, hepatic
diseases, cardiac failure, surgical operation, inflammatory disease.
Modifying the cut-off, is possible to obtain higher specificity with lower
sensibility without reach an acceptable compromise. An inconclusive review
evaluated the utilise of DD as clinic parameter to exclude PE without other
diagnostic tests (14).
Several reasons cause problems with the dosing and the clinical interpretation
of DD in patients with symptoms of PE because: 1.the presence of other diseases
that, activating the coagulation, cause the presence of DD,
2.the onset of symptomatology,
3.last but not least the rate cost/efficacy suffer of the prevalence of the
disease (16, 17) and therefore it shall be used in the case of low prevalence
alone or in association with venous Doppler and with arterial blood gas (19).
Venous Doppler of inferior leg –
PE and DVT of inferior leg can be considered as part of an unique clinic identity
defined “venous thromboembolism”. Autoptic studies have demonstrated that
90% of patients with PE have thrombosis inferior leg veins.
The presence of DVT in patients with a suspected PE is an element that induce
to start anticoagulant therapy and makes unuseful performing other invasive
evaluation. Reports have demonstrated that B-Mode exam, integrated with the
colour Doppler method, is very useful in venous thrombosis up the knee (20).
The failed squeezing of venous vessel is the higher specificity diagnostic
criteria, while intralumen hyperecogenicity and the alteration of colour Doppler
signal have less diagnostic value (20). Moreover several studies demonstrated
that the clinical diagnosis of DVT is poorly applicable, allowing to diagnose
correctly in less of 50% of cases. In spite of the majority of patients with
PE that shows no signs or symptoms of DVT, the specificity of Doppler test
is high (97%).
Moreover Doppler study shows a thrombosis in 30 –50% of patients with proved
PE, and therefore the test has an higher specificity and poor sensibility.
A normal Doppler test does not exclude the presence of PE. Some Authors suggest
to perform an inferior leg veins Doppler test when, in presence of a clinical
suspect, the scintigraphy test is negative. In the event that Doppler test
is negative, the thromboembolic risk is so low to permit the stop of anticoagulant
therapy. In order to improve the sensibility of Doppler in these patients,
newer diagnostic protocol are needed.
In conclusion first step non invasive test can be useful in confirming the
suspect of PE, waiting the exact diagnosis.
Spiral CT pulmonary
scan –
The CT spiral scan is able to recognise the embolus at pulmonary trunk and
at segmentary arteries, showed as filling defect. The percent of subsegmentary
emboli is about of 6% and they are very dangerous in patients with a compromised
cardiopulmonary reserve.
Of course the CT technique is simpler quicker than the angiography one. The
sensibility and the specificity for the segmentary vessels is high (92%) (23
– 25), for this reason its use is recommended in:
1.Patients with suspect of PE with severe clinical presentation (syncope,
hypotension, shock, or improvised dyspnoea. 2.Presence of anomaly at the chest
x-ray
3.Non diagnostic scintigraphy
4.Negative colour Doppler in patients with a compromised cardiopulmonary reserve
Spiral CT pulmonary scan is indicated in patients with discrepancy with scintigraphy
and clinical presentation, an with negative colour Doppler and normal cardiopulmonary
reserve.
In conclusion it is very difficult to consider the spiral pulmonary CT scan
as the gold standard; a certain advantage is the chance to diagnose a pulmonary
disease different from PE. Its role is important in the severe pictures (25,
26).
Pulmonary Scintigraphy
-
Pulmonary scintigraphy has a key role in the diagnosis of PE, being largely
evaluated in clinical trial. Theoretically the simultaneous acquirement of
ventilatory and perfusion images allows to show perfusion defects in presence
of a normal ventilatory phase, elements that consent a certain differential
diagnosis in conditions where ventilatory and perfusion defects can coexist.
Recent data from the PISAPED (27) study showed a high predictive positive
and value of perfusion scintigraphy when clinical suspect is elevated. An
important limit of scintigraphy test is the large variability from two performers
that can reach the 10 – 20%. During the scintigraphy test the images are acquired
in six projection. In the ventilatory phase various sketching can be used
like carbon particle marked with 99-tecnezium or 133 xenon.
For the perfusion phase albumin particle marked with 99 tecnezium are used,
which in presence of normal perfusion allocate uniformly in all the vascular
three.
I the PIOPED (11) study an “elevated probability” scintigraphy is associated
with pulmonary embolism in 96% of cases, but in patients with “low probability
“ test it has been demonstrated the presence of PE in 40% of patients. In
PISAPED (27) study it has been used just perfusion scintigraphy and the diagnosis
of PE has been posted in presence of perfusion defects of one or more segments
in order to eliminate intermediate probability test.
According to this classification, a positive scintigraphy has a positive predictive
value of 95%, while a negative test has a negative predictive value of 81%.
According to these studies a normal scintigraphy excludes PE in 95% of cases
and an “elevated probability” is coupled in almost 90% of cases.
A shallow zone is constituted by low and intermediate probability tests, which
are about 70%. In these patients the scintigraphy does not contribute to the
definitive diagnosis and only the simultaneous clinical evaluation and finding
of embolus origin can address the diagnosis. When the scintigraphy is associated
with a low clinical suspect the probability that the patient is affected by
PE is lower than 5%.
Clinical findings, chest x-ray echocardiography, Doppler and laboratory test
can help to increase the diagnostic suspect, but as already said have a limited
predictive value.
Prospective studies have demonstrated that the presence of a negative pulmonary
scintigraphy identifies a low risk population in which the anticoagulant therapy
can be stopped. When the pulmonary scintigraphy is inconclusive, a PE has
been demonstrated in 25% of cases. In these patients an ulterior diagnostic
deepening is needed before any definitive therapeutic option.
Pulmonary Angiography
– It is an invasive technique which is considered as the diagnostic gold standard
of PE. (Figure 2). It is a technique with risk of mortality (0.5%) (28), it
is not available in all the hospitals and presents difficult interpretation
even with expert radiologist and in the subsegmentary forms it is not so exact
as deemed (29 – 30).
It is useful in severe picture of PE where after the spiral CT pulmonary scan
an immediate diagnosis is necessary in order to start the thrombolitic therapy;
post angiography haemorrhage are high but not important quod vitam.
The angiography can be used in patients with low cardiopulmonary reserve and
when the previous images does not demonstrate PE, especially when a discrepancy
between the clinical presentation and scintigraphy is observed. Validate algorithms
to reduce the utilise of angiography has been approved (31).
Inferior leg venography
–
The rationale of its utilisation in the diagnosis of PE is due to the fact
that in 70% of cases the origin of embolus is in the inferior leg veins. The
findings of DVT authorise to start the anticoagulant therapy. Although considered
the gold standard for the diagnosis of DVT, the inferior leg venography is
able to show a proximal DVT in 60% (31, 32), moreover it can not be used in
case of allergy to the contrast and even if there is the protection of fetus,
and the limitation to the extension of the pelvis vessels, some people does
not accept the test during pregnancy.
CLINICAL DIAGNOSTIC MODELS
Several studies
have demonstrated the necessity to distinguish in clinical practise some subgroups:
1. Frequency: 4-5% of cases
Circulatory collapse or hypotension associated to lost of conscious; chest
pin can be present, muscle fatigue, orthopnoea, jugular turgidness. The Ecg
often shows classic alteration of PE, chest x-ray is often normal, blood gases
analysis shows hypocapnia associated to an important hypoexmia on responding
with oxygen therapy at 40%;
Clinical exam demonstrates a tricuspid systolic murmur increased by the inspiration
and a reinforced second tone on pulmonary with a systolic murmur. The echocardiogram
is useful to confirm the diagnosis, showing a right ventricle dysfunction.
The septum hypertrophy addresses for chronic dysfunction. T is important to
exclude: acute myocardial infarction, fulminate pneumonia, septic shock, cardiac
tamponade, aortic dissection. Massive haemorrhage and severe hypokalemia.
2. Frequency: 60% of cases
Two or more of the following symptoms: pleura chest pain, dyspnoea, deteriorating
of dyspnoea, emottisis, tachypnoea, tachycardia. In these patients chest x-ray
can show signs considered significant of pulmonary haemorrhage or infarction
and located in the site of chest pain.
The echocardiogram is often normal and the angiography shows peripheral emboli
with a moderate occlusion of vascular bed. Often blood gases analysis is normal
and radiologic alteration vanish rapidly (1 – 8 days) without arriving to
pulmonary infarction.
Alternative diagnoses are a numerous group including viral and bacterial pulmonary
infections, pneumonia, postoperative atelectasy, acute bronchitis, pericardium
and pleura inflammation, oesophagus spasm. Chest pain is not modified with
the respiration. Very difficult is the differential diagnosis with patients
suffering of COPD. Of course this is the most numerous group of patients with
the greatest diagnostic difficulties.
3.Frequency: 25% of cases
Recent appearance isolate dyspnoea. The thrombus is central and this reflects
on blood gases analysis which is always altered. Tachypnoea is often present.
Sign of pulmonary hypertension can be present.
Pressure is always normal in patients with normal cardiopulmonary reserve.
Ecg anomalies are absent, chest x-ray is often negative and it is useful to
perform an echocardiography test in order to exclude a right ventricle dysfunction
that makes worse the prognosis. Therefore an acute dyspnoea in a patients
with risk factors shall suppose a PE.
4.In remaining 10% of cases
This group of patients includes elderly people who present an opacity at chest
x-ray associated with dyspnoea and previous DVT. A very little group is constituted
by patients with poor functional reserves: these patients are defined by a
chronic pulmonary disease or symptomatic cardiac disease with acute failure
due to the PE.
In these cases the Ecg, chest x-ray and blood gases analysis are unuseful
because reflect the origin pathology.
Often the embolism is recurrent with an high mortality for the unknown diagnosis
and the interpretation of scintigraphy is very difficult. An angiography should
be necessary. Pulmonary CT spiral scan is poorly diagnostic. This is a little
numeric group that causes great diagnostic problems.
Francesco
Imperatore
Servizio di Anestesia e Rianimazione,
Dipartimento di Emergenza
e Accettazione Azienda Ospedaliera
di Rilievo Nazionale “A. Cardarelli”, Napoli
