Key facts:
Authors: Ruth de Souza and Ricky Jones
Top Tip: In massive PE, give rt-PA immediately; don't wait for imaging
Key Differential Diagnoses
- Pneumonia
- Exacerbation COPD
- Myocardial infarction
Note: there are many causes of a raised D-dimer, including these
Key Investigations
- ABG (± D-dimer, if being used as a ‘rule out' test)
- FBC, CRP, U+E, LFT, Bone, Glucose
- ECG, CXR
- CTPA (= 'rule in' test; within 1h in ?massive PE) or V/Q scan
Key Treatment
- OXYGEN, if hypoxic
- SC ENOXAPARIN 1.5 mg/kg od (or SC TINZAPARIN 175 u/kg od)
- PO WARFARIN 10 mg od day 1, then according to INR
- In ?massive PE, IV ALTEPLASE (rt-PA) 10 mg over 1-2 mins, followed by 90 mg over 2h (don't wait for imaging)
- If peri-arrest, and ?PE, give IV ALTEPLASE anyway
- In cardiac arrest, keep doing CPR
Key Management Decisions
- Thrombolysis
- Thoracotomy/embolectomy
Background
NO SINGLE NON-INVASIVE TEST for PE is both sensitive and specific. Some tests are good for 'ruling in' PE (eg CTPA) and some tests are good for 'ruling out' PE (eg D-dimer); others are able to do both but are often nondiagnostic (eg V/Q scan). There is no perfect test. If in doubt, treat
Introduction
- PE is one of the most important diagnoses not to miss in Acute Medicine. PEs usually arise from the deep veins of the pelvis or leg. Most PEs are small, physiologically insignificant, and asymptomatic
- They often occur in high risk patients (obese, female etc), after a period of immobility (especially surgery)
- Even when present, symptoms are nonspecific and vary in frequency and intensity, depending on the extent of pulmonary vascular occlusion and pre-existing cardiopulmonary function
- Larger emboli cause acute dyspnea, pleuritic chest pain, or both. Dyspnoea may be intermittent. Less common symptoms include cough and haemoptysis
- Multiple small PEs can present as SOB, or SOB on exertion; with no pain
- The first symptom in an older patient may be altered mental status
- Massive PE presents with hypotension, tachycardia, syncope, or cardiac arrest. MI and aortic dissection are alternative diagnoses
- If you are considering PE, and unless an alternative diagnosis can be made, treat the patient - pending investigation
- There is no perfect test for a PE. Hence its important to understand the clinical risk assessment (see below). Even though CTPA is currently 'the best' test to 'rule in' a PE, this too has problems. For example, it can miss small subsegmental PEs (30% of all PEs; these are known to predict recurrence, which might be fatal next time). Also, they may miss a PE, if it was more than a week ago, as the body dissolves the clot
- Mortality is 15% in the first 3 months after diagnosis. In nearly 25% of patients with PE, the initial clinical manifestation is sudden death (ie like MI, many die before hospital). Approximately 10% of symptomatic PE episodes are fatal within 1 hour of symptom development
- 10% are due to malignancy (often unsuspected; ie look for it). In these patients, 10% are alive at one year (ie it's a 'bad sign')
- Infected PEs also occur: 'normal PEs' can become infected; or they can be secondary to endocarditis = either R sided endocarditis, or 'paradoxical' L sided with a septal defect allowing emboli into the pulmonary circulation
- NICE CG144 (June 2012) concerns the investigation and treatment of PE, and the role of thrombophilia testing
- If you think your patient has had a massive PE, give rt-PA immediately, don’t wait for a CTPA
Definition
- Blockage of the pulmonary artery or one of its branches, usually occurring when a venous thrombus becomes dislodged from its site of formation and embolises to the pulmonary artery (or branch)
- Can also be caused by amniotic fluid, fat, air, sepsis (abscess), tumour cells
Epidemiology
- Incidence: 1/1000 per annum
- 2nd commonest cause of unexpected death in most age groups
- May contribute to 15-20% deaths in an acute general hospital
- Fatal PE occurs in about 0.5% of patients undergoing elective general surgery, 2-3% of those undergoing elective hip replacement, and up to 4-7% of those undergoing surgery for a fractured hip; with the biggest peak on days 1-3
Causes
- Usually secondary to lower limb DVTs
- Rarely, R ventricular thrombus (post MI)
- Very rarely, amniotic fluid, fat, air, sepsis (abscess), tumour cells
- Venous catheters
Risk factors
- Immobility (long journeys)
- Surgery (especially pelvic, hip or leg)
Notes: 50% occur on days 1-3. This is a very nice review article regarding when all postop complications occur, including PE, in general surgical patients: [Ref] . Though in another (orthopaedic study), 70% of VTE occurs after discharge from hospital: [Ref] - Oral contraceptive/pregnancy
- Female sex
- Obesity
- Neoplasia (especially pelvic)
- Recent MI or CVA
Types
- Peripheral
- Central
Note: each presents quite differently
Symptoms
- Small: SOB, infarction causes pleuritic chest pain, haemoptysis, occasionally pleural effusion
- Massive: dyspnoea, collapse/shock with little pain
Note: recurrent PEs can present as chronic pulmonary hypertension + RHF
Key questions
- "When did the chest pain start?"
- "Are you SOB?"
- "Any calf swelling, surgical operations or long journeys recently?"
- "Have you, or your family, ever had a PE or DVT before?"
Signs
- Nil, or
- Sinus tachycardia (can be only sign)
- Pleuritic rub (rare)
- Raised JVP
- Cyanosis
- Shock (in massive PE)
Clinical risk assessment
Three questions to be asked in determining clinical probability:
- Does the patient display the clinical syndrome of pulmonary embolism?
- Does the patient have a major risk factor for PE?
- Is PE more likely than any of the differential diagnoses in this patient?
- High probability = Yes to all three questions
- Intermediate probability = Yes to question 1 and one other
- Low probability = Yes to only question 1
The problem with PEs
- Diagnosis is challenging, because symptoms and signs are nonspecific and diagnostic tests are either imperfect or invasive
- The diagnosis is made on clinical assessment and collating investigations, understanding their positive and negative predictive value
Investigation
In a low-risk patient, a -ve D-dimer has a good negative predictive value
In a high-risk patient, a D-dimer is unnecessary and a CTPA is required
Blood
- FBC, CRP, U+E, LFT, Bone, Glucose
- ABG [Ref]
(A normal Po2 in room air does not rule out PE: BestBETs: Normal Po2 in room air as a rule out for PE, 2009), D-dimer (a good 'rule out' test):
In a low-risk patient, a negative D-dimer has a good negative predictive value([Ref] ) - In a high-risk patient, a D-dimer is unnecessary and a CTPA is required
- D-dimer is unreliable if patient is infected, pregnant, or has ARF/CRF, PVD or cancer
Note: infected pulmonary emboli also occur
Other
CXR
- This is done mainly, to exclude other diagnoses, eg pneumothorax
- A normal CXR, in an acutely hypoxic patient = PE until otherwise proven (or opportunistic pneumonia)
- 70% normal or minor atelectasis (usually missed)
- Small pleural effusion, usually unilateral
This CXR shows bilateral pleural effusions with long linear bands of atelectasis (Fleischner lines)
- There are several other radiological eponymous signs:
- 'Westermark Sign' = Dilatation of pulmonary vessels proximal to PE along with collapse of distal vessels, often with a sharp cut off
- 'Hampton's Hump' = pleural-based wedge shaped area of increased opacity. Hampton's Hump refers to an dome-shaped, pleurally-based opacification in the lung due to pulmonary embolism and lung infarction. It was described by Aubrey Otis Hampton but why the Hump? This characteristic appearance is seen because the infarcted pulmonary arteries cause a wedge-shaped infarction but because the bronchial arterial circulation is preserved, the expected apex of the wedge is spared causing a rounded/Hump-like opacification rather than a wedge
- 'Knuckle Sign' = prominence of central pulmonary artery with abrupt tapering
- 'Palla's Sign = enlargement of the right descending pulmonary artery
ECG
- Usually normal, or sinus tachycardia
- Occasionally RBBB, RAD, R ventricular strain; atrial fibrillation
- 'S1,QIII,TIII' is very rare; overdiagnosed as it is normal to have a (small) Q and an inverted T in III
Note: in massive PE, usually only sinus tachycardia and small complexes
ABG
- Normal, or pure hypoxia, often with hypocapnoea
Key investigation = CTPA (and its problems)
- CTPA (if underlying pulmonary disease, CXR abnormal, V/Q scan equivocal, or as easy to get as V/Q)
- Although CTPA is the 'best' 'rule in' test, this (and all tests) have problems, with a small but significant false +ve and -ve rate: [Ref]
- In ?massive PE, obtain imaging on ONE HOUR (but don't wait to give rt-PA), or
- V/Q scan (if high clinical risk, and normal CXR / no known lung disease)
- Doppler US legs occasionally (if clinically has DVT, V/Q or CTPA will be unlikely to change management or are contraindicated)
Note: 50% patients with PE, have no DVT on US; so negative test does not exclude PE
CTPA (massive PE)
Specialist investigations
Blood (if young, recurrent, or no obvious precipitant)
- Thrombophilia screen = Protein C/S, Antithrombin III, Antiphospholipid antibody, ANA/dsDNA,
- Factor V Leiden, lipoprotein A, homocysteine
Other
- ECHO sometimes useful in ?massive PE, if CTPA not available (again don't wait for ECHO to start rt-PA, if suspect diagnosis)
- Magnetic resonance angiography (MRA) is an alternative to CT angiography for patients who cannot tolerate contrast and for pregnant patients
- Pulmonary angiogram (if still uncertain after CTPA); this may be important, say, in a young woman, who needs to decide whether to use OC Pill or not, and who may may need thromboprophylaxis in pregnancy. So, pulmonary arteriography is indicated, when:
- pretest probability of PE is moderate or high and noninvasive tests are inconclusive
- the need to make or exclude the diagnosis is urgent, such as in an acutely ill patient
- anticoagulation is contraindicated
- chronic thromboembolic pulmonary hypertension is suspected
Differential diagnoses
- Pneumonia
- Exacerbation COPD
- Myocardial infarction
- LRTI
- Pneumothorax
- Pericarditis
- Musculoskeletal/rib fracture
- Of shock (especially MI, aortic dissection)
- Infected PEs (see above)
Treatment
Treatment (first line)
Drugs
- SC ENOXAPARIN 1.5 mg/kg od or SC TINZAPARIN 175 u/kg od
- PO WARFARIN 10 mg od on day 1 and then according to protocol and INR when confirmed. Usually 3-6 months. Lifelong if no obvious cause, family history, recurrent emboli or irreversible underlying precipitant present
Procedures
- IV line
- Sit up
- OXYGEN to achieve SpO2 of 95 – 97%, if hypoxic
PE and Oncology
- In patients with 'active' carcinoma (and relatively poor prognosis), and PE, there is now a trend to the use of LMWH (rather than WARFARIN) for medium/long term treatment
- [Ref]
- [Ref]
Prescribing issues
- If you send a patient home on WARFARIN, explain the 'do's' and 'don't's; preferably, give them some written information too
Key management decisions
- Thrombolysis/not
- ITU/not
Stop
- Oral contraceptive
Treatment (second line)
- In ?massive PE with haemodynamic instability, thrombolysis is justified (don't wait for imaging). If peri-arrest, and ?PE, give anyway (would be good for MI too; MI is main differential diagnosis with this presentation)
- IV ALTEPLASE (rt-PA) 10 mg over 1-2 mins, followed by 90 mg over 2h; max 1.5 mg/kg if patient [Ref]
- Or, thoracotomy + embolectomy
- If unwell, urinary catheter, CVP line, arterial line
- Consider vena caval filter if recurrence on adequate anticoagulation or if anticoagulation is contra-indicated
Prescribing issues
- Round up ENOXAPARIN dose to 20, 40, 60, 80 or 100 mg od
Admit?
- Most patients with PE should currently be admitted for initial treatment. Though some patients with a small PE can be managed as an OP, if haemodynamically stable (see below)
Bed plan
- Medical admission ward
- ± Respiratory
± ITU
Referral
- Respiratory, if no obvious cause or recurrent
- ± ITU (massive)
- ± Haematology, if suspect thrombophilia
The Rest
Small PEs, in well patients, can be safely managed as an outpatient; they may still need investigation for the cause of the PE
Maxim
- "The first three causes of SOB with a clear CXR are PE, PE and PE"
Complications
- Infected PE
- Pleural effusion
- Haemodynamic compromise, shock etc
- Severe hypoxia
Prognosis
- There is a 15% mortality in the first 3 mths (especially if present with hypotension, or immobilisation after a medical illness)
- 3.6% chance of major bleeding: [Ref]
- In one large study, the 30 day mortality was 17.4% in patients who were thrombolysed, and 8.6% in those who were not: [Ref]
Risk stratification
(who an be managed as an outpatient)
2°Prevention + Health Promotion
- Warfarin; tell patient do's and don't's, and how long for (usually 3-6 mths, or lifelong)
- Give out patient information leaflets
- Vena caval filter (esp when PE in pregancy; to prevent PE in next pregnancy)
- Advice re risk factors, eg: long journeys, obesity, surgery, oral contraceptive, pregnancy etc
- Note: there are SIGN (2002), RCOG (2004) and NICE (2010) on the prevention of thromboembolism
Follow-up
- Anticoagulation
- Respiratory, especially if recurrent, unexplained, or suspicious of underlying malignancy
- Haematology (if suspect clotting disorder)
Don't forget
- There is no single reliable non-invasive test
- A normal CXR, in an acutely hypoxic patient = PE until otherwise proven (or opportunistic pneumonia)
- If you think of it, treat it; even in non-massive ?PE. In ?massive PE, give rt-PA immediately; and definitive imaging in ONE HOUR is mandatory
- D-dimer is the best 'rule out' test
- CTPA is the best 'rule in' test. But even CTPAs can be wrong
- 10% are due to malignancy (often unsuspected). So, if no obvious cause, look for an underlying carcinoma (especially pelvic)
- If younger, and no obvious cause, look for thrombophilia
- Like ACS, even though PE/not seems simple, it is not, - so, involve seniors early
Red flags
- Shock
- Recurrent, or no obvious cause
