Pulmonary embolism

Pulmonary embolism (PE) is a commonly considered but relatively uncommonly diagnosed

condition in hospitalized patients. It is important to have an adequate understanding of the
pathophysiology as well as a rapid and reliable strategy of investigation and management. This
is particularly important in intensive care unit (ICU) patients where diagnosis can be difficult
and PE may be life threatening, with mortality rates in hemodynamically unstable patients
being about 30%.
Early deaths in PE are usually the result of acute right ventricular (RV) failure and
cardiogenic shock.
After the first few days, mortality is less common and mostly determined by recurrent
thromboembolic events and the underlying disease state.

AETIOLOGY
Deep venous thrombosis (DVT) and PE are components of a single disease termed venous
thromboembolism (VTE).
Embolization of DVT to the pulmonary arteries leads to PE. The incidence of VTE in the
population is about 1 in 1000 per year and is more common both with advancing age and in
males.
Most PE results from DVT of the lower limbs, pelvic veins or inferior vena cava (IVC),
although DVT of the upper limbs, right atrium or ventricle does occur. Up to 40% of patients
with DVT develop PE, although if the DVT is isolated to below the knee then clinically
obvious PE is rare.
Predisposing risk factors for VTE involve one or more components of VIRCHOW’S
TRIAD :

(1) venous stasis, (2) vein wall injury, and (3) hypercoagulability of blood.
The main factors are immobility (from any cause), surgery, trauma, malignancy, pregnancy and
thrombophilia.
VTE can be recurrent, which should prompt investigation for thrombophilia.
This is a group of inherited conditions associated with a high incidence of VTE.
The most important of these is activated protein C resistance, which is mediated by the factor
V Leiden mutation.
Up to 50% of patients with recurrent VTE episodes (as well as 20% of patients with a single
episode) have this condition; however, its association appears to be greater with DVT than
with PE.
Up to 5% of patients with VTE develop chronic pulmonary hypertension.
Risk factors for venous thromboembolism
Primary hypercoagulable states (thrombophilia)
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
Resistance to activated protein C 
(inherited factor V Leiden  mutation)
Hyperhomocysteinaemia
Lupus anticoagulant (antiphospholipid 
antibody) Secondary hypercoagulable states
Immobility Surgery
Trauma
Malignancy
Pregnancy and the puerperium
Obesity
Smoking
Estrogen-containing  oral  contraception  or 
hormone  replacement therapy
Indwelling catheters in great veins and 
the right heart
Burns
Patients with limb paralysis (e.g. spinal 
injuries)
Heart failure
Increasing age
PATHOPHYSIOLOGY
The effects of PE range from being incidental and clinically irrelevant to causing severe
obstruction to the pulmonary circulation and sudden death. Pulmonary arterial obstruction
and the subsequent release of vasoactive substances such as serotonin and thromboxane A2
from platelets lead to elevated pulmonary vascular resistance and acute pulmonary
hypertension. Acute pulmonary hypertension increases RV afterload and RV wall tension,
which leads to RV dilatation and dysfunction, with coronary ischaemia being a major
contributing mechanism.
In massive PE, the combination of coronary ischaemia, RV systolic failure, paradoxical
interventricular septal shift and pericardial constraint leads to left ventricular (LV)
dysfunction and obstructive shock.
In patients with underlying cardiorespiratory disease, a small PE can have profound
consequences.
Pulmonary arterial obstruction causes a mismatch between lung ventilation and perfusion,
which leads to hypoxaemia.
The ventilation of lung units that have reduced or no perfusion causes increased deadspace
ventilation and an increase in the end tidal to arterial CO2 gradient.
Alveolar hyperventilation also occurs, leading to hypocapnia.
Increased right atrial pressure can open a patent foramen ovale, which may result in righttoleft
shunting, manifested as either refractory hypoxaemia or paradoxical (arterial)
embolisation, commonly to the brain, leading to cerebral infarction.

CLINICAL PRESENTATION
PE is relatively uncommon in critically ill patients despite the frequent presence of risk factors
for VTE.
However, when PE does occur the diagnosis is frequently overlooked or is difficult to confirm
because several more prevalent cardiopulmonary diseases, including heart failure, pneumonia
and chronic lung diseases, have similar clinical features.
Up to one in six patients have the diagnosis made more than 10 days after symptom onset.
Clinical assessment should raise the suspicion of PE but is neither sensitive nor specific enough
to reliably confirm or exclude the diagnosis on its own.
A number of clinical decision rule (CDR) systems have been developed, the most widely
reported of which are the Wells’ score and the Geneva score.
These CDRs use a combination of symptoms, signs and risk factors to stratify patients into
different disease probability categories.
CDRs provide accurate and reproducible determinations of probability and outcome for use in a
diagnostic or therapeutic strategy.
Patients can therefore have their probability determined as unlikely (in whom PE can be safely
ruled out with a negative D-dimer result) or likely (in whom an imaging test is required and in
whom prompt anticoagulant therapy should be considered).
Differential diagnosis of  pulmonary embolism
Acute myocardial infarction
Acute coronary syndrome
Acute pulmonary oedema
Pneumonia
Asthma or exacerbation of chronic obstructive 
pulmonary  disease
Pericardial tamponade
Pleural effusion
Fat or amniotic fluid embolism
Pneumothorax
Aortic dissection
Rib fracture
Musculoskeletal 
pain Anxiety

SYMPTOMS
Dyspnoea, pleuritic chest pain, and haemoptysis are the classic symptoms of PE. Most patients
will have at least one of these symptoms, with dyspnoea being the most common. The
combination of pleuritic chest pain and haemoptysis reflects a late presentation where
pulmonary infarction has occurred. If syncope occurs, and there is no other obvious cause, it is
likely that this is a massive PE. A family history of venous thrombosis makes an inherited
thrombophilia likely.

PHYSICAL SIGNS
Physical signs can be absent, but the most frequent sign is tachypnoea. Others include
tachycardia, fever and signs of RV dysfunction (raised jugular venous pressure, parasternal
heave and loud pulmonary component of the second heart sound). In massive PE, signs may
include hypotension, pale mottled skin and peripheral or even central cyanosis. It is important to
examine for signs of DVT, particularly in the legs.
INVESTIGATIONS
The diagnosis of PE requires a high level of clinical suspicion and the appropriate use of
investigations. The aim of these investigations is to confirm or exclude the presence of PE, but
also to stratify treatment accordingly. The optimal investigation strategy depends upon the
individual patient and institution; however, multidetector computed tomographic pulmonary
angiography (CTPA) scanning is now the imaging test of first choice. A suggested investigation
algorithm is shown in Figure 34.1.

D-DIMER
The serum Ddimer level, which becomes elevated when acute thrombus formation occurs, is
useful for exclusion of VTE, particularly when it is normal and combined with a lowrisk
clinical assessment.8 Because of its sensitivity, negative Ddimer tests, particularly using
enzymelinked immunosorbent assays (ELISA), enzymelinked immunofluorescence assays
(ELFA) and latex quantitative assays, are highly predictive of the absence of both DVT and PE.
A high Ddimer concentration is also an independent predictive factor associated with
mortality.9 Unfortunately, Ddimer levels are often elevated in ICU patients for reasons
including infection, inflammation, cancer, surgery and trauma, acute coronary syndrome,
stroke, peripheral artery disease or ruptured aneurysm. Ddimer tests should be used with
caution in patients who are elderly (as the upper limit of normal increases with age), who have
prolonged symptoms and who are already receiving therapeutic anticoagulant therapy.
TROPONIN, BRAIN NATRIURETIC PEPTIDE (BNP)  AND NT-
TERMINAL PRO-BNP
Although of little use for confirming or excluding the diagnosis, measurement of troponin, BNP or NTproBNP can assist
in risk stratification of patients with diagnosed PE. A raised troponin is associated with haemodynamic instability in
patients with nonmassive PE independently of clinical, echocardiographic and laboratory findings.10 Raised troponin
also predicts a higher mortality.11 Low levels of BNP and NTproBNP have been shown to correlate with an uneventful
course in patients with known PE.12 NTproBNP appears to be a better predictor of outcome than troponin.13

ARTERIAL BLOOD GASES
A normal arterial blood gas profile does not exclude the diagnosis of PE; however, hypoxaemia
(with a widened alveolar–arterial oxygen gradient), hypocapnia and an increased endtidal CO2
gradient should raise the suspicion of PE, even if these are common findings in critically ill
patients for other reasons. Metabolic acidosis may be present if shock from a large PE occurs.

ELECTROCARDIOGRAPH
A normal electrocardiograph (ECG) is found in about onethird of patients. Apart from sinus
tachycardia (which is nonspecific), the most frequent ECG abnormalities are nonspecific S–T
depression and Twave inversion in the anterior leads, reflecting right heart strain. The pattern of
a deep Swave in lead I and a Qwave and inverted Twave in lead III (S1Q3T3) is classical, but
infrequently present. Other possible ECG abnormalities include left or rightaxis deviation, P
pulmonale, right bundlebranch block and atrial arrhythmias. The ECG is also useful in
excluding acute myocardial infarction and pericarditis.

CHEST X-RAY
The chest Xray is often normal or only slightly abnormal, with nonspecific signs such as cardiac
enlargement, pleural effusion, elevated hemidiaphragm, atelectasis and localised infiltrates.
More specific findings, including focal oligaemia, a peripheral wedgeshaped density above the
diaphragm and an enlarged right descending pulmonary artery, are uncommon and difficult for
nonradiologists to identify. The chest Xray is also useful in identifying an alternative diagnosis
such as pneumothorax, pneumonia, acute pulmonary oedema, rib fracture and pleural effusion.

IMAGING TESTS INCLUDING CTPA SCAN
Imaging is required in any patient with a high or likely clinical probability. As the technology
has improved, CTPA scanning, especially the multidetector scanner (MDCTPA),14 has now
largely replaced lung ventilation– perfusion (V/Q) scanning as the costeffective and clinically
reliable imaging procedure of choice in patients with suspected PE.15 This is because the
CTPA scan has the advantages of greater diagnostic accuracy, ready availability at most
hospitals, more rapid image acquisition time, and the possibility of making an alternative
diagnosis. Highresolution images to the level of segmental and in some cases subsegmental
pulmonary arteries can be obtained in a short time period (often a single breathhold). When
compared with conventional angiography it appears reliable, with excellent sensitivity,
specificity and accuracy.16 It is therefore recommended that the CTPA scan should be the
principal imaging test for patients with high and moderate probability of PE.
Although inconclusive CTPA scans occur in around 10%, a negative CTPA result means that
withholding anticoagulant therapy is safe.17 An emerging problem of CTPA scanning,
however, is the increased detection (around 10%) of small peripheral emboli in subsegmental
pulmonary arteries due to better visualisation of these arteries. The clinical significance of these
findings in critically ill patients is unknown; however, these are usually unlikely to lead to a bad
outcome if left untreated. The CTPA scan can also be used to assess the severity of PE. An
increased RV/LV ratio18 and clot in the proximal branches of the pulmonary artery19 correlate
with the clinical severity of PE. Severity stratification is further increased by combining CTPA
scanning with other tests such as troponin10 and BNP or NTProBNP.12 CTPA scanning may
also identify the causative DVT in the veins of the legs, pelvis and abdomen or detect
alternative or additional diagnoses such as a pulmonary mass, pneumonia, emphysema,
pneumothorax, pleural effusion or mediastinal adenopathy (Fig. 34.2). Despite the increased use
of the CTPA scan, the V/Q scan retains a role when CTPA is either unavailable or
contraindicated (e.g. significant renal impairment, anaphylaxis to intravenous contrast or
pregnancy).20 V/Q scanning also allows quantification of regional blood flow within the lungs,
which may be required in the assessment of chronic pulmonary venous embolism. PE may also
be diagnosed by gadoliniumenhanced magnetic resonance pulmonary angiography (MRA). In
some series as many as 25% of examinations have been regarded as noninterpretable.21
ECHOCARDIOGRAPHY
Because of its portability, echocardiography has the greatest usefulness in critically ill patients
with probable PE. Many patients with PE have an echocardiographic abnormality, the most
common being RV dilatation, RV hypokinesis, paradoxical interventricular septal motion
toward the LV, tricuspid regurgitation and pulmonary hypertension. The pattern of RV
hypokinesis with apical sparing is considered pathognomonic for PE.22 The presence of RV
dysfunction correlates with mortality.23 However, it must be noted that a negative
echocardiography does not exclude PE. Transthoracic echocardiography will also allow
estimation of pulmonary arterial pressure, identification of intracardiac thrombi (which usually
requires surgical embolectomy) and aids in differential diagnosis by excluding aortic dissection
and pericardial tamponade. Transoesophageal echocardiography has the additional benefit of
directly identifying embolus in the proximal pulmonary arteries, which is common in patients
with haemodynamically significant PE. Echocardiography has its best application in
haemodynamically unstable patients, where it can be rapidly brought to the patient. If the
patient has RV dilatation and hypokinesis in the right clinical setting, PE is extremely likely.

DIAGNOSIS OF DVT USING ULTRASOUND
Doppler ultrasound has been recommended to search for DVT in the leg veins, from where over
90% of emboli originate. If a leg DVT is confirmed, anticoagulation is required unless the DVT
is entirely below the knee, where the associated morbidity is low. Ultrasound is highly accurate
in symptomatic or proximal DVT, although in asymptomatic patients ultrasound is much less
likely to find DVT, meaning the absence of a DVT does not exclude PE. The best use of
ultrasound is when a CTPA scan is contraindicated.24

INVESTIGATION STRATEGY IN  HAEMODYNAMICALLY 
STABLE PATIENTS
• A CTPA scan is the preferred initial test and, if positive, the patient should be stratified into
high or moderate risk. The presence of clot within pulmonary arteries confirms the diagnosis of
PE.
• An echocardiograph should then be considered to assess RV dysfunction for highrisk patients
who have: – clot within proximal pulmonary arteries – raised RV/LV ratio (i.e. >0.9–1.0) –
raised troponin, BNP or NTproBNP.
• If a CTPA scan is not possible (contraindicated or unavailable), an alternative investigation,
such as a V/Q scan, MRA or ultrasound should be considered.
• None of these tests excludes PE, but a negative result in a haemodynamically stable patient
means that the outcome without anticoagulation is unlikely to be poor.

INVESTIGATION STRATEGY IN  HAEMODYNAMICALLY 
UNSTABLE PATIENTS
• An echocardiograph (preferably transoesophageal) should be the first test performed.
• If the patient has acute RV dilatation and visible embolus, PE is confirmed.
• If there is RV dilatation but no visible embolus, then a CTPA scan is required depending on
how unstable the patient is. • If there is no RV dilatation, the haemodynamic instability is
unlikely to be due to PE (although this cannot be excluded completely). Efforts towards finding
an alternative diagnosis are the priority.
• If echocardiography is not readily available, a CTPA scan should be performed.
MANAGEMENT
MANAGEMENT PRINCIPLES
Once PE has been confirmed patients at all levels of severity should receive anticoagulation
with either unfractionated or lowmolecularweight heparin (LMWH) to prevent further
embolisation. In more severe cases of PE, however, the key principle is embolus destruction to
maximise a more rapid effect on relief of RV dysfunction. To assist in planning management, it
is important to grade the severity of PE. Prediction models based on clinical findings at
diagnosis may be useful for the prognostic assessment of patients with acute PE. The
Pulmonary Embolism Severity Index is the most extensively validated prognostic clinical
score25 and a simplified version of this has been recently developed.26 The place of these in
critical illness is yet to be determined and it may be that a combination of a predictive scoring
system with a diagnostic test is the most useful.27

MASSIVE PE (HAEMODYNAMICALLY UNSTABLE)

Patients with PE and hypotension have an approximately 30% mortality rate despite treatment.1
If cardiopulmonary resuscitation is required, this increases to 65%. These patients have the
most to benefit from a strategy that includes attempts at urgent embolus destruction (with
thrombolytic therapy or embolectomy), concurrent haemodynamic support and prevention of
further embolisation.

SUBMASSIVE PE (HAEMODYNAMICALLY UNSTABLE WITH

EVIDENCE OF RV DYSFUNCTION)
Patients with PE and evidence of RV dysfunction have higher mortality (around 15%) and
recurrence rates than those with normal RV function.23 They also develop shock and RV
thrombi more frequently. These patients require prevention of further embolisation but also
warrant strong consideration of embolus destruction using thrombolytic therapy. Thrombolytic
drugs appear to improve outcomes,28 although this appears to be at the expense of a higher
bleeding risk.29 The presence of RV dysfunction (to meet the submassive classification) can be
confirmed using echocardiogram but can also be inferred from evidence of RV dilatation on
CTPA scanning or by raised troponin, BNP and NTproBNP, all of which have been shown to
predict higher mortality.30

MILD PE (HAEMODYNAMICALLY STABLE WITH NO RV

DYSFUNCTION)
Patients with PE who have normal blood pressure and normal RV function (determined by
echocardiography or CTPA scan) have a low risk of death or recurrence. The predominant
management goal is prevention of further embolisation using anticoagulant therapy, as
treatment focused on embolus destruction is unlikely to confer additional benefits. In summary,
the major principles of management are therefore:
• prevention of further embolisation (for all of massive, submassive and mild PE)
• embolus destruction (for massive and submassive PE)
• concurrent haemodynamic support (only required in massive PE). A suggested management
strategy is outlined in Figure 34.1.

PREVENTION OF FURTHER EMBOLISATION
ANTICOAGULANT THERAPY Heparin has been known to prevent recurrence and reduce the
mortality from PE for over 40 years. LMWHs are as effective and safe as unfractionated
heparin31 and may even be better.32 LMWHs offer several advantages over unfractionated
heparin, including a longer halflife, increased bioavailability, a more predictable dose– response
and fewer requirements for monitoring and dose adjustments. They should be readily used in
the stable patient with PE.
Unfractionated heparin should be used in patients with renal impairment, and following
thrombolytic therapy or embolectomy, as it can be easily and rapidly reversed. Intravenous
unfractionated heparin should be administered after a bolus and initial monitoring should be
with 6hourly activated partial thromboplastin time (APTT) testing. Since subtherapeutic levels
of anticoagulant therapy increase the risk of recurrence, it is important to achieve therapeutic
heparinisation rapidly. Weightbased dosing of heparin should be used as target anticoagulation
levels are reached sooner33 (Table 34.1). The predominant complications of both
unfractionated heparin and LMWHs are bleeding related. These include bleeding peptic ulcer,
stroke, retroperitoneal haematoma and postsurgical wound haemorrhage. Heparininduced
thrombotic thrombocytopenia syndrome (HITTS) can also occur. Bleeding complications and
HITTS appear to be less common when LMWHs are being used. A number of conditions are
considered to be relative contraindications to anticoagulant therapy. These include active peptic
ulceration, recent surgery, recent trauma and recent cerebral haemorrhage. In each individual
patient the risktobenefit ratio (taking into account the severity of the PE) should be considered
before anticoagulation is withheld from the patient. Oral anticoagulants should be started as
soon as possible so that LMWH or unfractionated heparin can eventually be ceased. For
warfarin, this is generally when the international normalised ratio is >2.0. Although warfarin
has been commonly used as the longstanding anticoagulant of choice, adverse events leading to
hospitalisation remain common.34 New oral anticoagulants, including rivaroxaban (which
competitively binds activated factor X) and dabigatran (a direct inhibitor of thrombin) have
been developed.35,36 These drugs have more rapid onset of action and more predictable
anticoagulant effects meaning fixed dosages and no routine laboratory coagulation monitoring.
Large studies have found that rivaroxaban is noninferior to a LMWH/warfarin combination37
and dabigatran is noninferior to warfarin.38 The place of these drugs in critically ill patients
with PE remains unknown.
 Weight-based dosing of intravenous heparin
INITIAL DOSING

Loading 80 units/kg

Maintenance infusion 18 units/kg per hour

Perform APTT in 6 hours

SUBSEQUENT DOSE ADJUSTMENTS

APTT DOSE CHANGE (UNITS/KG PER HOUR) ADDITIONAL ACTION NEXT APTT

<35 seconds +4 Rebolus of  80 units/kg 6 hours

35–45 seconds +2 Rebolus of  40 units/kg 6 hours

46–70 seconds Nil Nothing 6 hours

71–90 seconds −2 Nothing 6 hours
>90 seconds −3 Stop infusion  for 1 hour 6 hours

Adapted from Raschke et al.33 APTT = activated partial thromboplastin 
time.

INFERIOR VENA CAVA FILTER

Inferior vena caval (IVC) filters are another method used to prevent further embolisation. They
may also be useful as primary prevention, although safety and efficacy have not been firmly
established. IVC filters are indicated for patients in whom anticoagulation is contraindicated
and those who experience recurrent PE despite adequate anticoagulation.39 They may have a
role in patients with massive or submassive PE who have undergone open surgical
embolectomy or thrombolysis. Insertion is usually performed percutaneously in a radiology
department, but it can be done at the bedside. They lower early recurrence rates but increase
longterm DVT recurrence rates.40 Newer retrievable designs may be more efficacious and more
safe if removed at the appropriate time.
Absolute indications include:
• new or recurrent PE despite anticoagulation
• contraindications to anticoagulation
• complications resulting from anticoagulation.
Other recommended indications include:
• patients with extensive DVT
• patients following a surgical embolectomy
• patients following thrombolytic therapy.

EMBOLUS DESTRUCTION
THROMBOLYTIC THERAPY
Intravenous thrombolytic drugs result in dramatic and immediate haemodynamic improvement
in some patients by dissolving the embolus and rapidly reducing pulmonary arterial obstruction.
Experimental studies, clinical observations and randomised trials have consistently
demonstrated the favourable effects of thrombolytic therapy on angiographic, haemodynamic
and scintigraphic parameters of patients with acute PE, although comparisons with patients who
received heparin have essentially revealed similar degrees of embolus resolution after a few
days to a week. A large multicentre patient registry found that patients receiving thrombolytic
therapy (clearly on an ad hoc basis) for PE had lower rates of mortality and recurrence than
patients receiving heparin.41 Despite this, no randomised study has demonstrated that
thrombolytic therapy improves survival over standard anticoagulation, most likely because
studies have been underpowered. A metaanalysis found that thrombolytic therapy for PE was
associated with a nonsignificant reduction in recurrent PE or death when compared with
heparin.29 A significant survival benefit in favour of thrombolytic therapy was demonstrable
when analysis was restricted to those studies that included massive PE. It is therefore
recommended that once the diagnosis has been confirmed thrombolytic therapy should be given
without delay to patients with massive PE unless there is a clear contraindication.42 Around
90% of patients should respond to thrombolytic therapy.43 The clinical benefits and relative
underuse of this therapy have been recently highlighted using nonrandomised data.44 There is
also justification for the use of thrombolytic therapy in patients with submassive PE as a
randomised study found a significant reduction in the requirement for emergency escalation of
treatment, although without an effect on survival.28 It would also seem appropriate to give
thrombolytic therapy to patients with demonstrable intracardiac thrombus. There is a large array
of thrombolytic drugs with few comparative studies. Although there may be slight differences
between thrombolytic drugs, the choice of drug is less important than the choice to give
thrombolytic therapy at all. Suggested doses are recommended in Table 34.2, and this can be
administered through either a peripheral or a central venous catheter. In contrast to acute
myocardial infarction, thrombolytic therapy may be useful in PE when given up to 14 days after
symptoms begin.45 Once the thrombolytic therapy has been administered, heparin should be
commenced. Haemorrhagic complications are not uncommon and can significantly affect
patient morbidity; however it is difficult to predict those patients who are at the highest risk for
bleeding. Major clinically significant bleeding can occur in up to 10% of patients, although
cerebral haemorrhage is fortunately uncommon (0.9%).46 Recent surgery is not an absolute
contraindication and patients should have their individualised risks and the benefits weighed up;
in shocked patients with massive PE the balance appears to be in favour of thrombolytic therapy
for almost all patients. If bleeding occurs, the thrombolytic therapy should be ceased, fresh
frozen plasma should be given to replace coagulation factors and an antifibrinolytic drug (such
as aprotinin) should be commenced.
Recommended doses of thrombolytic drugs  for pulmonary embolism
Urokinase 4400 units/kg bolus (over 10 minutes) followed by 4400 units/kg per hour for 12 hours

Streptokinase 250000 unit bolus (over 15 minutes) followed by 100000 units/hour for 24 hours

Alteplase 10 mg bolus followed by 90 mg over 2 hours

Reteplase 10 unit boluses 30 minutes apart

SURGICAL EMBOLECTOMY
The merit of surgical pulmonary embolectomy, which has traditionally been seen as a lifesaving
option for moribund patients with massive PE, has been questioned since the advent of reliable
thrombolytic therapy. Embolectomy surgery results vary widely and there has traditionally been
an associated perioperative mortality of 25–50%. There is little reliable evidence comparing
embolectomy and thrombolytic therapy. Mortality rates have been found to be lower when
using a surgical approach combining rapid diagnosis, prompt surgical intervention and a high
frequency of concurrent IVC filter placement.47 Surgical embolectomy should therefore be
strongly considered in patients with PE and hypotension who have absolute contraindications
to thrombolytic therapy, or if thrombolytic therapy has failed.42 It may also be useful when
patients have freefloating intracardiac thrombus.
PERCUTANEOUS EMBOLECTOMY
Percutaneous pulmonary embolectomy methods include either embolus extraction techniques
(pure percutaneous embolectomy) or embolus disruption techniques (including catheterdirected
thrombolytic therapy and percutaneous thrombus fragmentation techniques).48 Success rates
have been over 80% with reasonable complication rates, mostly from singlecentre case series.49
Randomised studies comparing percutaneous embolectomy with systemic thrombolytic therapy
or systemic anticoagulation have not been done, so for now percutaneous embolectomy should
be considered in patients with contraindications to systemic thrombolytic therapy who are in
specialised centres.
CONCURRENT HAEMODYNAMIC SUPPORT
Shocked patients with PE (massive PE) need urgent haemodynamic support in addition to
attempts at embolus destruction and prevention of further embolisation.

INTRAVENOUS FLUIDS
Volume loading can improve haemodynamic status in patients with massive PE, although if
excessive then fluid therapy may worsen RV function, which can in turn affect LV function and
become detrimental.50
Cautious administration of small amounts of intravenous fluid should occur.

VASOPRESSORS
Ischaemia in the coronary circulation is an important factor in the haemodynamic instability of
massive PE.4 Embolus destruction (with thrombolytic therapy or embolectomy) should have the
greatest effect on ischaemia reduction. However, elevation of the blood pressure and reduction
in pulmonary and RV pressures may also be helpful, based on the rationale that the RV
coronary perfusion pressure (RVCPP) can be severely impaired in massive PE.
RVCPP is estimated by the formula:
RVCPP = MAP - RVPm (34.1)
where MAP is the mean arterial pressure and RVPm is the mean RV pressure, all in mmHg.
RVPm can then be estimated by the formula:
RVPm = CVP + 1/3 (PAPs – CVP) (34.2)
where CVP is the central venous pressure and PAPs is the systolic pulmonary arterial pressure,
all in mmHg. When RVCPP falls as low as 30 mmHg (4 kPa) (normal being around 70–80
mmHg (9.31–10.64 kPa)), RV myocardial blood flow falls substantially and this contributes
significantly to severe RV failure and shock. Efforts to elevate the MAP or reduce the PAPs
should increase the RVCPP and therefore improve coronary blood flow to relieve ischaemia.
Haemodynamic support for the shock state due to massive PE should therefore predominantly
involve vasopressor drugs as these will predominantly increase MAP, and therefore RVCPP.
Norepinephrine (noradrenaline) is preferred to a pure alpha agonist such as phenylephrine, as
cardiac output and RV myocardial blood flow effects are greater owing to the added beta-
adrenoceptor agonist action. Dopamine, epinephrine (adrenaline) and vasopressin are
reasonable alternatives to norepinephrine. Although systemic vasodilators might improve the
cardiac output in massive PE, they may be harmful overall as the MAP will either fall or remain
constant at best and therefore the RVCPP will not increase. Isoprenaline, dobutamine,
nitroglycerin, nitroprusside or milrinone should be considered only if the MAP is adequate and
treatment is focused on cardiac output or pulmonary artery pressure. Extracorporeal membrane
oxygenation (ECMO) is an extreme but alternative form of mechanical assistance that may be
available in more specialised institutions.51 It should be considered for patients with PE who
have had cardiopulmonary arrest or have very severe shock.

SELECTIVE PULMONARY VASODILATORS

Inhaled nitric oxide may be useful in patients with massive PE51 by selectively decreasing
pulmonary arterial pressure with minimal effect on systemic haemodynamics. It may also assist
in the severely hypoxaemic patient. Inhaled prostacyclin is an alternative.52

OTHER MANAGEMENT ISSUES

Oxygen should be supplemented to target adequate oxygen saturation. High flows may be
required because of hyperventilation and the increased dead space. Intubation and mechanical
ventilation are often necessary in patients with massive PE. If chest pain is prominent, morphine
should be administered. To guide resuscitation, it is useful to have at least a central venous
catheter, particularly before thrombolytic therapy is given. Although there is increased risk of
bleeding owing to the concurrent administration of thrombolytic therapy and/or anticoagulant
therapy in these patients, this is probably outweighed by the importance of secure venous access
and monitoring of the circulation in patients with haemodynamic compromise due to PE.

PREVENTION
Prophylaxis is probably the most important management aspect of VTE. All ICU patients
should have an adequate assessment as to whether prophylaxis is warranted, although most
should receive it using pharmacological thromboprophylaxis.39 Careful attention to the
intervention and dose is required, as omission of prophylaxis53 and failure of prophylaxis54 are
common. LMWHs have challenged traditional prophylaxis with fixed lowdose subcutaneous
unfractionated heparin such that both are suggested alternatives for the prevention of VTE in
critically ill patients.39 Both therapies seem comparable for prophylaxis of DVT; however,
rates of PE and HITTS were lower in a recent large study.55 Mechanical approaches (including
graduatedcompression stockings and intermittent pneumatic compression devices)56 seem best
utilised in patients who are bleeding or at major risk of bleeding. When bleeding risk decreases,
pharmacological thromboprophylaxis should be commenced.