Pulmonary Embolism

Pulmonary embolism (PE) is an obstruction in part of the pulmonary arterial tree. The obstruction has usually travelled from a distant site, via the venous system. Pulmonary embolism is an important cause of dyspnoea, chest pain or collapse; it is a life-threatening condition which is easily missed.¹

Most pulmonary emboli are thrombotic in nature. Other, rarer causes are: fat embolism, following long bone fracture or orthopaedic surgery; amniotic fluid emboli; and air embolism, following neck vein cannulation or bronchial trauma.¹

The rest of this article deals with thrombotic pulmonary embolism. This is part of the disease entity venous thromboembolism (VTE), comprising deep venous thrombosis (DVT) and pulmonary embolism (PE).

For clinical purposes, PE is classified into 2 main groups:

• Nonmassive PE, where patients are haemodynamically stable.
• Massive PE, where the patient is shocked or hypotensive: this is defined as a systolic blood pressure <90 mmHg or a pressure drop of 40 mmHg for >15 min not caused by new-onset arrhythmia, hypovolemia or sepsis.

The annual incidence of known VTE in the Western World is 1.0 and 0.5 per 1000 respectively. There are 65,000 cases in hospital patients each year in England and Wales. The prevalence of unsuspected PE at post mortem is 3-8%, and has been unchanged for 3 decades; post-mortem meta-analysis showed that more than 70% of PEs were missed by the clinician.

• Clots form when one or more of the following factors are present: increased blood coagulability, reduced mobility, or blood vessel abnormalities. These correspond to the risk factors for VTE (see table).
• Some patients with dyspnoea or right heart failure have severe pulmonary hypertension due to silent recurrent PE (chronic thromboembolic pulmonary hypertension). This condition is probably a distinct disease entity, different from acute PE.^3,4

Pulmonary embolism presents in a variety of ways clinically: doctors need to be aware of the risk factors, maintain a high index of suspicion, and recognise the different presentations. PEs may be "silent", and many are diagnosed only at postmortem. Always suspect pulmonary embolism (PE) in sudden collapse 1-2 weeks after surgery.

Clinical scenarios¹

• Circulatory collapse in previously well patient: this is massive PE with right heart failure
• Pleuritic pain, possibly with haemoptysis
• Isolated dyspnoea, often of sudden onset
• Collapse in a frail patient; usually an elderly patient with poor cardiorespiratory reserve, where a relatively small PE can be catastrophic

Possible symptoms

• PE may be silent
• Dyspnoea and pleuritic pain are common
• Substernal chest pain also occurs in PE
• Haemoptysis
• Collapse or syncope
• Symptoms of hypoxia: anxiety, restlessness, agitation, impaired consciousness

Possible signs

• There may be none
• Tachypnoea and tachycardia are common signs
• Pleural rub
• Signs of right ventricular strain: raised JVP, right ventricular heave, gallop rhythm, atrial fibrillation, loud P2, pulmonary regurgitation murmur.
• Signs of DVT
• Fever (usually < 39°C)
• In massive PE: hypotension, cyanosis, signs of shock or impaired consciousness
• Cardiac arrest, classically with electromechanical dissociation but can be other forms

Difficulties in clinical assessment

• Dyspnoea, tachypnoea and tachycardia, which are common presentations, may be misinterpreted as anxiety or psychogenic hyperventilation.⁶
• Pleuritic pain is a common symptom with causes other than PE. Traditionally, it has been thought that musculoskeletal causes are likely, if chest wall tenderness on palpation reproduces the patient's pain. However, one study found that this sign was of no diagnostic use.⁷
• Doctors are advised to be aware of risk factors, but PE also occurs in those with a low risk profile.^5,8
• In primary care, one author has used exercise pulse oximetry to assess likelihood of PE.⁸

Risk score

Assessment of the clinical probability of VTE is recommended, as it is relevant when interpreting clinical findings and deciding how to investigate. Various VTE risk scores are available: BTS recommends the Wells score for use by junior doctors² (Wells' score was not designed for use in primary care). Other scoring systems have also been developed.^9,10

Other causes of collapse, chest pain or dyspnoea, importantly: acute coronary syndrome, aortic dissection, cardiac tamponade, pneumonia, pneumothorax, septicaemia, endocarditis. Aortic dissection is important to distinguish, because it is better not anticoagulated.

Note: treatment may precede investigations if patient is very ill (see initial management)

General investigations³

• Baseline investigations as for any ill patient: oxygen saturation, FBC, biochemistry, baseline clotting screen.
• ECG may be normal, or show any of these changes: sinus tachycardia, atrial fibrillation, non-specific ST or T wave abnormalities, right ventricular strain pattern V1-3, right axis deviation, RBBB, or deep S-waves in I with Q waves in III and inverted T waves in III ('S1,Q3,T3' pattern). A large PE can show ECG features of acute cardiac ischaemia (e.g. ST depression).¹²
• Chest XRay - mainly useful to exclude other chest disease, and is needed for interpreting V/Q scans. It is usually normal, but may show: decreased vascular markings (so-called "Westermark sign"), atelectasis, or a small pleural effusion. An occasional late sign may be a homogeneous wedge-shaped area of pulmonary infarction in the lung periphery - Hampton's hump (with its base contiguous to a visceral pleural surface and its rounded convex apex directed toward the hilum).
• Arterial blood gases may show reduced PaO₂, reduced PaCO₂ due to hyperventilation, or acidosis.
• Echocardiography may show thrombus in proximal pulmonary arteries, and if normal can exclude haemodynamically important PE.² It can be useful as a bedside test in critically ill patients with cardiovascular compromise, but cannot exclude smaller PEs. It may show signs of right ventricular strain or RV hypokinesis, the latter signifying submassive PE.
• Cardiac troponins can be indicative of right heart strain. Some authors suggest they can be helpful in distinguishing patients with submassive PE, who are at higher risk of deterioration.^13,5 However, their usefulness is debated, and echocardiography seems more helpful.¹⁴

Specific investigations for VTE²

The choice and order of investigations will depend on the clinical likelihood of PE, how ill the patient is, and availability of the test. The "gold standard" test is conventional pulmonary angiography, but this is invasive and usually unavailable urgently.
Investigation strategies are detailed as part of the initial management and pregnancy sections below. An explanation of the scope of each test helps in understanding these strategies:

• Leg ultrasound: In patients with co-existing clinical DVT, lower limb ultrasound as the initial imaging test is often sufficient to confirm VTE - and hence to start anticoagulation. However, a singe normal leg ultrasound cannot exclude DVT.
• D-dimers: Only a normal result is of any clinical value. Abnormal results do not imply an increased likelihood of PE, because other factors can raise D-dimer levels, notably postoperatively,⁵ pregnancy¹⁵ and infection e.g. cellulitis. D-dimer assay should only be considered after assessment of clinical probability. It should not be used in those with high probability of PE, because it is not specific enough to exclude PE in that situation. (This is the BTS recommended strategy, but has been debated.^16,17) Each hospital should provide information on the sensitivity/specificity of its D-dimer test, as various assays are available.
• Isotope lung scanning (V/Q scan): Although there have been controversies about the accuracy of isotope scans, they are reliable enough to exclude or confirm PE if performed according to UK protocols.^2,5 However, if the result is 'indeterminate', further imaging is needed.
• Computed tomographic pulmonary angiography (CTPA): This has good sensitivity/specificity and is quick to perform. It is increasingly used. CTPA can also be extended to detect DVT.

Explanation of initial management strategies^2,3

• Thrombolysis is effective, but must be balanced against risks of bleeding: therefore, it is the first line treatment for massive PE, and may be given on clinical grounds alone if cardiac arrest is imminent.^2,18 It can be given in cardiac arrest during CPR, and may be life-saving in this situation.
  
  The use of thrombolysis in submassive PE is controversial, and it should not be used first-line in nonmassive PE.³

  Contraindications to thrombolysis3 Absolute contraindications (but BTS guidelines say that even absolute contraindications may be less important in a life-threatening situation): Active internal bleeding Recent spontaneous intracranial bleeding Most other contraindications should be considered relative in massive PE:3 Major Surgery, delivery, organ biopsy or puncture of non-compressible vessels within 10 days Ischaemic stroke within 2 months GI bleed within 10 days Serious trauma within 15 days Recent CPR Platelet count <100 000/mm3; prothrombin time <50% Neurosurgery or ophthalmological surgery within 1 month Pregnancy, bacterial endocarditis, uncontrolled severe hypertension Diabetic haemorrhagic retinopathy

• Plasma expanders/fluid bolus and inotropic support: it is common practice to use these as supportive treatments for massive PE. The evidence for plasma expanders tends to suggest they may be harmful rather than beneficial, and ESC guidelines suggest they should be limited to 500 ml.³ Pulmonary vasodilators are probably helpful, and conversely, drugs causing pulmonary vasoconstriction may be harmful.^3,18
• With absolute contra-indications to thrombolysis, or where it has failed, in a critically ill patient the alternatives are: surgical embolectomy;^21,22 and catheter embolectomy or clot fragmentation via a catheter.^18,20,22 These require special expertise and are not widely available. Extracorporeal life support has also been used.²³
• IVC filters may be used where anticoagulation or thrombolysis is contraindicated, and can be inserted at the bedside. Their benefit is debated.^2,19

Further management²

• Oral anticoagulation should only be started after confirmed VTE. The target INR is 2.0-3.0, after which heparin can be stopped.
• Anticoagulation is continued for 3-6 months, depending on the cause of the PE and continuing risk factors. This can be shortened to 6 weeks if the PE was due to a temporary condition.²
• Recent research suggests no extra benefit from 6 months' compared to 3 months' anticoagulation.²⁸
• In patients at high risk of recurrence, or with proven recurrence, anticoagulation may be continued indefinitely; this is decided on an individual basis, balancing the risk of bleeding against the risk of recurrent VTE.²
• IVC filters are controversial, but may be used if there is high risk of DVT recurrence and anticoagulation is contraindicated.²

PE is both important and more difficult to assess in pregnancy, because:

• Both pregnancy (any gestation) and the puerperium are risk factors for VTE.
• PE is the leading cause of pregnancy related maternal death in the developed world.
• Physiological symptoms which are common in pregnancy can mimic PE: e.g. shortness of breath, chest pain.
• Fetal exposure to unnecessary radiation and drugs should be avoided.

Investigations^15,29

• In seriously ill patients, a bedside echocardiogram, if available, is the first test.
• Ultrasound is a good first-line investigation to look for DVT: if positive, then anticoagulation without further investigation may be appropriate.
• Chest XRay with lead shield should be performed to exclude other causes.
• If ultrasound and chest XRay are normal, and the patient has no history of lung disease including asthma, a half dose lung perfusion scintigram is used. If lung disease is present or the chest XRay abnormal, CTPA should be performed. (Both of these tests incur radiation exposure to the fetus, but at a dose thought to be reasonable; CTPA has the disadvantage of exposing mothers, particularly the breast tissue, to high doses of radiation.)

Treatment^2,15

• Warfarin is teratogenic and should be avoided.
• Heparin is considered safe; but check manufacturer's instructions, because some preparations contain benzyl alcohol. Of the LMWHs, dalteparin, enoxaparin and tinzaparin are considered safe. Further information on heparin dosage in pregnancy is available.¹⁵
• Detailed guidance is available regarding the use of heparin around delivery and postpartum.¹⁵
• Anticoagulation should continue for 6 weeks after delivery or for 3 months after the PE, whichever is longer.
  

  Emergency management of massive PE in pregnancy RCOG guidelines are:15 Collapsed patients need to be assessed by a team of experienced clinicians, including the oncall consultant obstetrician, to decide on an individual basis whether to give intravenous unfractionated heparin, thrombolytic therapy or thoracotomy and surgical embolectomy. Intravenous unfractionated heparin is the preferred treatment in massive PE with cardiovascular compromise. The on-call medical team should be contacted immediately. An urgent portable echocardiogram or CTPA within 1 hour of presentation should be arranged. If massive PE is confirmed or, in extreme circumstances prior to confirmation, immediate thrombolysis should be considered. One regimen for the administration of intravenous, unfractionated heparin is: Loading dose of 80 units/kg, followed by a continuous intravenous infusion of 18 units/kg/hour. If a woman has received thrombolysis (see below), the loading dose of heparin should be omitted and an infusion started at 18 units/kg/hour. Activated partial thromboplastin time (APTT) must be measured 4-6 hours after the loading dose, 6 hours after any dose change and then at least daily when in the therapeutic range. The therapeutic target APTT ratio is usually 1.5-2.5 times the average laboratory control value. Anecdotal evidence: various treatments have been successfully used in individual cases: thrombolysis,30 catheter fragmentation,31 and surgical embolectomy.32

• Mortality from PE is 30% if untreated, reduced to 2-8% by adequate anticoagulation and thrombolysis. There is a high mortality in the first few hours due to cardiovascular collapse. Cardiac arrest has a very poor prognosis.^2,3
• In the acute situation, right ventricular dysfunction on echocardiography, raised cardiac troponins and acidosis carry a worse prognosis.¹³
• Right heart failure can occur acutely or later; in the longer term, pulmonary hypertension, right heart failure - which in turn can cause left ventricular failure - are possible complications.
• There is a considerable risk of recurrence in the first 4-6 weeks,³³ and adequate anticoagulation can reduce this by 75% to <8%.³ The prognosis of non-massive PE depends mainly on the existence of other factors such as age, COPD, IHD or cancer.^3,33
• Systemic emboli can occur if there is a cardiac septal defect.
• Complications of anticoagulation: with LMWH as initial treatment and oral anticoagulation to an INR of 2-3, the rate of major bleeding at 3 months is 3% and mortality is 0.3%.³³
• Chronic thromboembolic pulmonary hypertension may be a consequence of recurrent small emboli, or alternatively may be a different disease entity from acute PE. Untreated, it has a poor prognosis, being usually fatal within 3 years of diagnosis. Endarterectomy (in specialised centres) is the treatment of choice.⁴

Prevention of deep vein thrombosis in at-risk patients is important, and recent NICE guidance is available.³⁴