Pulmonary embolism refers to an obstruction within the pulmonary vascular tree. This can be from several causes:
Amniotic fluid (though pathophysiology may be obstruction in nature)
The majority of cases involve a thrombotic pathology which will be the primary discussion here. This is the main feared complication of deep venous thrombosis (DVT) and with it they are termed venous thromboembolic (VTE) disease. DVT is covered elsewhere (here) and many of the key points are very relevant here as well.
As well as differentiation by pathology as noted above, an important differentiation is based on the clinical effects of the obstruction. This has significant impact on subsequent management.
Massive PE - this is an acute PE with obstructive shock or hypotension (SBP <90mmHg) Submassive PE - an acute PE without obstructive shock but with features of right ventricular dysfunction Non-massive PE - an acute PE that does not meet either of the above criteria and can be considered as lower risk.
The pathophysiology of DVT is discussed in more detail in those notes, and is worth understanding. The important pathology of PE relates to the impact of the embolism on the cardiac and respiratory functions.
After thrombus formation, usually within one of the deep veins of the legs, a fragment of this thrombus breaks off. This clot travels along the major veins, into the right side of the heart and passes through, lodging within a pulmonary vessel (the location will be dependent on the size of the thrombus) Blood flow through this vessel and so to distal lung regions ceases or is significantly reduced. This creates alveolar dead space (lung that is ventilated but not perfused - one part of the spectrum of V/Q mismatch). Shunting of blood around the blockage can occur due to the highly recruitable nature of pulmonary vessels, so there may be minimal impact in the case of small embolisms (hence some PEs being clinically insignificant/asymptomatic). Hypoxia probably develops despite (or because of this shunting) as it seems likely that it means that the lungs are no longer able to appropriately match the ventilation and perfusion of lung units. Some units will get more perfusion than their ventilation can oxygenate, and so some incompletely oxygenated blood passes through the lungs to the arterial side, resulting in hypoxia. There may also be a number of inflammatory mechanisms that are triggered by the embolism that have additional effects on impairing lung function.
However, in larger blockages their may be a significant obstruction to flow. This resistance can result in an elevation of pulmonary arterial pressures, which feeds back to the right ventricle. This resistance can be compounded by reactive hypoxic vasoconstriction which is aiming to redirect blood to better oxygenated regions of the lung, and other vasoconstricting substances released in response to the insult of the PE e.g. serotonin. Due to the less muscular anatomy of the right ventricle, increases in afterload in this way can result in dilation, and in severe cases precipitate right heart failure. Coronary ischaemia can also occur in this situation, further contributing to myocardial dysfunction.
The V/Q mismatch can have an impact on respiratory parameters. Compensatory hyperventilation can occur, perhaps triggered by the inflammatory nature of the embolism. This can lead to a hypocapnia that can be detected on ABG, and be clinically apparent as a tachypnoea.
Loss of blood flow to a lung segment can result in pulmonary infarction.
As with DVT, the spectrum of the presentation can be very varied, from asymptomatic through to cardiac arrest. In cases of symptoms, they may include:
Shortness of breath
The presentation may be of cardiovascular collapse/compromise, with variation from a syncopal episode, dizziness to cardiac arrest. Chest pain from PE is traditionally described as being pleuritic in nature.
The signs of PE are also often nonspecific and can include:
Split second heart sound - gallop rhythm
Given the spectrum of compromise that may be present, the approach will be guided by how sick the patient is. 3 rough categories may be considered (although these are points along a spectrum)
Patients with cardiac arrest will undergo simultaneous assessment and treatment as per ALS algorithms and guidance. The identification of PE as the likely cause of the cardiac arrest will impact on conduct of the arrest management.
An acutely ill patient with a significant PE may present with cardiovascular, respiratory or neurological compromise. An A to E systematic approach will likely be applicable here to allow prioritised assessment and treatment of life threatening issues.
Patients who are more stable may be assessed in a more conventional approach, with a careful history, examination, and targeted investigations.
With the different presenting complaints, a number of routine investigations are likely to be useful in the assessment process:
Bloods: FBC, U&E, troponin, D-dimer, BNP
A CXR can be useful in assessing other causes of dyspnoea. A CXR in PE may well show no clear changes, but in some case may demonstrate:
wedge density (from pulmonary infarct),
segmental reduced blood marking (oligaemia),
small pleural effusion.
An ECG will frequently be normal. Some changes that may be present include:
Features of right heart strain
S1Q3T3 (classic but not very common)
ST segment changes
T wave inversion
Right axis deviation
An ABG may show a respiratory alkalosis, hypoxia, and/or metabolic acidosis (from CVS compromise).
Cardiac blood tests (Troponin, BNP) can be useful in cases of assessing for other pathology, but also have a role in cases where a PE is present. A raised troponin level in patients with PE can indicate myocardial dysfunction/injury and can contribute to risk assessment. Similarly, a normal BNP reading can provide some reassurance about the degree of cardiac strain resulting from the PE.
Additional, more specialised investigations may be indicated in these cases:
The computerised tomography pulmonary angiogram (CTPA) is the key investigation in diagnosing PE. Its availability and high accuracy allow it to have high rates of rule-in and rule-out, and can also allow diagnosis of alternative pathology. Inconclusive results can still occur (about 10%). A problem may arise from these benefits in that they are able to detect small (subsegmental) emboli, the clinical significance of which is unclear. It can also help identify high risk factors in PE e.g. right ventricular enlargement.
A Ventilation perfusion (V/Q) scan, was previously used more frequently in the investigation of PE, but is now more frequently used in cases where CTPA is contraindicated (e.g. contrast allergy, pregnancy).
Echocardiography can be useful in assessing for PE, especially in cases of CVS compromise.
Given the frequent vagueness and variability of the presentation of PE, similar diagnostic challenges are present as with DVT. As such, similar stratified assessment approaches have been described to enable appropriate use of more invasive investigations (CTPA) whilst still allowing an appropriate degree of sensitivity. NICE recommend the use of a two-level PE Wells’ score to allow risk stratification in patients in whom a clinical assessment suggest that PE may be a diagnosis.
In patients with a ‘likely’ Wells’ score, they should undergo a CTPA.
In patients with an unlikely Wells’ score, they should undergo a D-dimer. If this is negative, then consideration should be given to other diagnoses. If this is negative, then patients should progress to CTPA.
In the case of a negative CTPA, other diagnoses should be considered. A positive CTPA will allow a diagnosis of PE to be made.
The PERC rule is another tool that can help with risk stratification. In this case, it can identify low risk patients who do not need further investigation. It is used in patients who are already deemed to be low risk, but can provide further confidence of that low risk and remove the need for D-Dimer testing. The tool can be accessed here: https://www.mdcalc.com/perc-rule-pulmonary-embolism
As noted above, this will be dictated by the degree of compromise of the patient. The principles of management are:
Prevent further embolism
Removal of embolism (massive and possibly submassive)
Cardiovascular support (massive)
This results in two main classes of pharmacological treatment:
There are also interventional treatments for embolectomy which may be available at certain centres.
Each clinical case is clearly unique, but some general guidance can be considered as: Massive PE - thrombolysis or embolectomy Submassive PE - consider thrombolysis/embolectomy - bleeding risk needs to be considered and benefits may be less clear Non-massive PE - treat with anticoagulation
Factors that denote higher risk in the submassive PE category include:
RV dysfunction on Echo
Increased RV to LV ratio on CTPA (>0.9-1.0)
Clot within proximal pulmonary artery (on CTPA or Echo)
The goal of this therapy is to prevent further embolism. The main drugs used may include:
Low molecular weight heparin (LMWH)
Unfractionated heparin (UFH)
Direct oral anticoagulant drugs (DOACs)
For most patients with a PE, LMWH will be the initial treatment. Fondaparinux is an alternative. UFH should be considered as an alternative in certain patients:
High bleeding risk (as more reversible)
Impaired renal function
Initially in unstable patients with thrombolysis
Patients should then be commenced on longer term anticoagulation. In many cases this will be warfarin. LMWH should be continued during warfarinisation for 5 days or until the INR in >2. Warfarin should be continued for at least 3 months, when the risk benefit can be reassessed. Patients with an unprovoked PE should be considered for a longer period of warfarin therapy. Patients with cancer and a PE should be treated with LMWH for 6 months before reassessing the risks and benefits.
Rivaroxaban is a DOAC that is recommended by NICE as an alternative for treating and prevention of PE.
This refers to systemic administration of drugs that act to cause clot breakdown. The activation of plasminogen (into plasmin) can result in rapid clot lysis with improvement in the pulmonary obstruction and resulting cardiovascular compromise. However, the risk of bleeding is inherent to this treatment (occurring in up to 10%). These risks limit this treatment to significant PEs only, which will generally mean massive PEs. There is debate about whether the benefits in submassive PEs justify their use, and it may be that this benefit outweighs the risks in certain patients.
This may be an alternative therapy, although will likely be limited to certain centres. This includes surgical and percutaneous techniques, with the latter including catheter directed thrombolytic therapy as well as clot disruption or removal.
In severe PE, physiological support may be needed. This will generally be similar to as required for other causes of organ compromise.
Cardiovascular support can be slightly challenging. An important component is to maintain an adequate coronary perfusion pressure, as cardiac ischaemia, particularly of the RV, is an important feature in the compromise of patients with a massive PE. However, certain pharmacological approaches to this can impact on already compromised cardiac output. Noradrenaline, adrenaline and vasopressin may be considered rather than pure alpha agonists. Systemic vasodilators may be helpful in improving cardiac output, but the impact on reducing MAP and RV coronary perfusion pressure can be detrimental.
ECMO may be a consideration in some centres for support in massive PE.
Inhaled nitric oxide and prostacyclin may be helpful in reducing pulmonary hypertension and thus easing RV strain.