PULMONARY EMBOLISM CHECKLIST

Introduction

Step 1: Think of the diagnosis

Step 2: Assess risk factors

Step 3: Local investigations

Step 4. Pre-test probability

Step 5. Dx tests and imaging

Step 6. Dx algorithm

Step 7. Treat the Patient

Rural recommendations

References

About this document

Introduction.

The paradox in diagnosis of pulmonary embolism (PE) is that it tends to be both under diagnosed and over-investigated.¹ 70% of emboli are diagnosed at autopsy. Even today, guidelines to investigations are variable and not always evidence based. In the rural setting many of these investigations are delayed or simply unavailable, yet a timely decision for or against anticoagulation needs to be made. Rural physicians have the advantage of knowing the patient better and can therefore better asses probability of disease prior to testing. We should have in house the capability of doing one simple test, which, if negative, can exclude the diagnosis in a patient with low probability of embolism. We can also do a few simple tests, which might support an alternative diagnosis. The rest of the investigation sometimes becomes less evidence based, but, given the following checklist, we should be able to appropriately pursue the diagnosis with the help of our imaging colleagues in our referral centres:

Step 1: Think of the diagnosis.

Avoiding under-diagnosis involves including PE in the differential. There are 5 identifiable syndromes:

1. Isolated dyspnoea and tachypnoea.

2. Pneumonic syndrome of pleuritic chest pain, cough, râles or hemoptysis.

3. Central catastrophe of shock, hypotension, right heart failure or sudden death. This is fortunately uncommon. Timely diagnosis is unlikely in a rural facility.

4. Chronic recurring emboli leading to pulmonary hypertension and right heart failure.

5. Septic emboli e.g. IV drug abuse or infected central catheter.

The first 2 syndromes are the most common and produce the findings which are most characteristic. 97% of patients with PE have either dyspnoea, tachypnoea or pleuritic pain.² Other symptoms or signs can include cough, fever, râles, leg pain and hemoptysis. If pneumonia or COPD with exacerbation is the diagnosis, PE should usually be thought of in the differential.

Step 2: Assess patient risk factors.

Avoiding under-diagnosis involves considering at higher risk any patient with features of Virchow’s triad: stasis, endothelial injury or hypercoagulability:

1. Within 4 weeks of Surgery

2. Pregnancy and Puerperium

3. Lower limb fracture or paralysis

4. Malignancy

5. Reduced mobility

6. Previous PE. Previous or current deep venous thrombosis (DVT)

7. Cardiovascular or pulmonary disease

8. Oral contraceptives or estrogen therapy

9. Coagulopathy

Step 3: Apply locally available less specific investigations.

These may provide an alternate diagnosis and avoid over-investigation.

1. Chest X-ray. Only 12 % of patients with PE have a normal chest radiograph. Atalectasis, parenchymal abnormality, pleural effusion, cardiomegaly or raised hemidiaphragm may be found, but these findings are neither sensitive nor specific. Lobar consolidation, however, suggests a diagnosis of pneumonia. Pneumothorax or pneumomediastinum can suggest an alternative diagnosis.

2. ECG. This is commonly abnormal in PE, but never diagnostic. ST changes suggesting pericarditis or infarction are helpful in providing an alternative diagnosis.

3. Blood Gases. Often hypoxia with respiratory alkalosis. Can be normal 15% of the time. In PE may indicate severity of illness, but unlikely to help with diagnosis. A finding of metabolic acidosis may suggest an alternative reason for dyspnoea and tachypnoea.

4. Pulmonary function tests. Often abnormal, but not specific or sensitive. Not recommended.

5. Echocardiogram. Often abnormal in PE and may be prognostic, but never diagnostic.³ Seldom easily available in rural practice. Not recommended.

Step 4. Apply steps 1-3 to determine pre-test probability.

This takes into consideration physical findings, risk factors and more probable diagnoses to yield the Wells Score (Table 1)

Moderate and high probability patients should be anticoagulated with Low Molecular Weight (LMW) Heparin while awaiting further investigation.

Step 5. Consider more specific testing and imaging:

D-dimer

Ventilation/Perfusion scan

CT Pulmonary angiography with proximal leg venography

Proximal leg ultrasound

Pulmonary angiography

1. D-dimer.

· The latex fixation test is not sensitive enough. The whole blood assay (SimpliRED) is recommended in patients with low pre-test probability to rule out the possibilty of PE in these patients. More highly sensitive ELISA tests are available, but have a higher false positive rate.⁵ Most rural areas should have access to the SimpliRED assay in house.

· All D-dimer tests are false positive more often in the elderly, recent surgery, and cancer, but such patients are more likely to have higher pre-test probability and therefore PE could not be excluded by D-dimer. This test has no predictive value in patients of intermediate or high pre-test probability.

· A negative SimpliRED D-dimer is sufficient to exclude diagnosis of PE in a low pre-test probability patient. A patient with a positive SimpliRED D-dimer should be anticoagulated with LMW Heparin while awaiting further investigation.⁴

2. Ventilation/Perfusion (V/Q) Scan

· Indicated only if chest x-ray is normal and there is no cardiovascular or pulmonary disease

· High probability scan makes the diagnosis of PE in the context of reasonable pre-test probability of PE.⁶ False positives can occur.

· Normal scan effectively excludes PE.⁶

· 65% of scans are non-diagnostic and require another test for exclusion.⁵ Proximal leg ultrasound weekly for 2 weeks is usually recommended, but difficult to schedule on time. It often does not get done, leading to unnecessary or prolonged anticoagulation or missed diagnosis. Rural patients are at a particular disadvantage in having to travel for multiple tests.

· More limited availability, especially out of hours and especially for some rural areas.

· Previously felt to be investigaion of choice in pregnancy. Modern CT now imarts less radiation exposure than V/Q scanning¹².

3. Computerized Tomography (CT) Pulmonary Angiography and proximal leg venography. This is not the same as chest CT or pulmonary angiography. Helical CT is done with rapid high-pressure contrast injection and imaging within a few seconds.

· Used if abnormal Chest X-ray (CXR), cardiovascular or respiratory disease.

· Some sources recommend this as initial imaging for non-massive PE.⁷ Good evidence for this approach is available from the PIOPED II study, which suggests that CT Pulmonary Angiography with venous phase imaging are sufficient to make the diagnosis provided clinical findings are not discordant.⁸ Advances in CT imaging are expected to steadily improve reliability.

· A positive study confirms PE.

· A negative scan is not equivalent to a normal V/Q scan and does not exclude PE.⁹ An additional study is required such as CT venography or proximal leg ultrasonography. The latter study is ideally repeated twice at weekly intervals.⁷

· Useful to obtain another diagnosis that would explain symptoms and exclude PE.

· CT venography done at the same time as CT pulmonary angiography takes little additional time and adds to sensitivity. It also identifies pelvic or abdominal thrombi that would otherwise be missed. There is larger exposure to both radiation and contrast. This combination is probably a good “one stop” resource for the rural patient who has to travel for each investigation and has faint hope of access to weekly leg ultrasounds as recommended in many guidelines.¹ The evidence for accuracy of this approach is supported by PIOPED II data. There are guidelines from the British Thoracic Society which suggest that CT pulmonary angiography is the best initial imaging modality.

· Occurrence of venous thromboembolism in patients with negative CT pulmonary angiography and negative leg ultrasound taken the same day and repeated in 1 week is as low as 1.5%.¹⁰ Study followup, however, was only for 3 months, and more robust data is needed. There are still no good outcome studies assessing CT venography with CT pulmonary angiography.

· Sometimes more available in centres taking rural referrals and more accessible out of hours. Timely imaging is always desirable.

· Caution is advised in renal failure, and contrast allergy, where V/Q scanning is usually preferred.

· Discuss pregnancy with the Radiologist. Many now feel that modern CT produces less fetal radiation exposure¹².

4. Ultrasound (U/S) of Proximal Leg Veins

· If clinical DVT is present, leg ultrasound can be the initial investigation. If positive it is sufficient to confirm PE.⁷

· This is a useful and non-invasive test, but it is often difficult to obtain a study at an appropriate time – especially for a rural patient.

· This is a recommended additional test for the patient with a non-diagnostic V/Q scan or a negative CT angiogram. If negative, a repeat is suggested at 1 and 2 weeks if pre-test probability is intermediate or high.

5. Pulmonary Angiography

· Still considered the “gold standard” for PE diagnosis, this study is reserved for patients at very high pre-test probability who have otherwise negative imaging and in whom suspicion for PE remains very high. This is the province of the consultant.

· Mortality as a result of the study can be up to 0.5%.

Step 6. Apply Steps 4 and 5 to the following algorithm to confirm or exclude a diagnosis of PE in your patient:

What is the pre-test probability?

· Low

· Intermediate

· High

Step 7. Treat the Patient.

The difficult work has been done. Apart from the rare unstable patient, all patients can be managed in a rural setting. The unstable patient needs rapid anticoagulation with unfractionated heparin and rapid transport for specialty evaluation and possible thrombolysis.

1. Patients with low pre-test probability and negative SimpliRED D-dimer should have another diagnosis pursued and have no treatment for PE.

2. Patients with a negative V/Q scan should have another diagnosis pursued and no treatment for PE.

3. Patients with intermediate or high pre-test probability need to have LMW Heparin started prior to any further imaging. If coagulopathy is suspected consider drawing blood for studies prior to anticoagulation.

4. Patients with confirmed PE (high probability V/Q scan, positive CT pulmonary angiogram/venogram or positive proximal leg U/S) should have warfarin added. Heparin can be discontinued on the fourth or fifth day following initiation of warfarin therapy, provided the INR has been therapeutic range (INR 2.0-3.0) for two consecutive days. This allows time for depletion of factors in the intrinsic clotting pathway. Recommended duration of warfarin use appears in Table 2:

5. Unstable patients are best anticoagulated more quickly with unfractionated heparin. It would require high pre-test probability with reasonable exclusion of alternate diagnoses (such as dissecting aneurysm) before consideration of anticoagulation in this event. Thrombolysis can be considered, but must await further imaging for diagnosis and will need to be considered in a referral centre.

6. Patients with another diagnosis receive alternative treatment.

Recommendations for rural physicians:

1. Exclude PE in a low probability patient with a negative SimpliRED D-dimer. All other patients need further workup.

2. Consider V/Q scanning in otherwise healthy patients with normal CXR, pregnancy, renal failure and contrast allergy, but remember that 65% of these will be non-diagnostic and will need leg ultrasound concurrently, and perhaps at 1 and 2 weeks. Scanning takes 4-5 hours, and ultrasound will be difficult to schedule. CT alone may impart lower radiation doses to the fetus than V/Q scanning ¹².

3. Strongly consider CT pulmonary angiography with proximal leg venography as your initial imaging investigation. It is more widely and immediately available and the initial venous imaging can be done at the same time. It is occasionally going to provide and alternate diagnosis. Some current guidelines would support terminating investigation if this were negative ^1,7 , however intermediate and high risk patients are still going to need followup U/S at 1 and 2 weeks if we consider the best evidence at present.

4. Take the trouble to follow patients with negative CT studies with proximal leg U/S at 1 and perhaps 2 weeks. This is often a scheduling nightmare, and primary physicians and consultants often overlook this step.

5. In summary: Low probability patients with negative D-dimer can be excluded. All other patients can be managed more simply and quickly by CT pulmonary angiography and proximal leg venography. Low risk patients if this study is negative can be excluded. All other patients should be considered for proximal leg U/S up to twice at weekly intervals.

References:

1. Iles S, Beckert L, Than M, Town I. Making a diagnosis of pulmonary embolism – new methods and clinical issues. New Zealand Medical Journal 2003;116: 1177.

2. Tabas J, Audio Digest Emergency Medicine Vol 19 issue 16. Aug. 21, 2002.

3. Geerts B, Demers C, Kearon C. Practical Treatment Guidelines – Suspected PE. The Thrombosis Interest Group of Canada. May 2004. Available at: http://www.tibc.org/ . Accessed Aug. 11, 2004.

4. Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, et al. Derivation of a simple clinical model to categorize patient’s probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost 2000; 83(3): 416-420.

5. Kearon C. Diagnosis of Pulmonary embolism. CMAJ 2003; 168(2): 183-194.

6. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA 1990; 263: 2753-2759.

7. Campbell A, Fennerty A, Miller AC. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003; 58: 470-484.

8. Stein PD, Fowler SE, Goodman LR, et al., for the PIOPED II investigators. Multidetector computed tomography for acute pulmonary embolism. NEJM 2006; 354: 2317-2327.

9. Perrier A, Howarth N, Didier D, et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Ann Intern Med. 2001 Jul 17; 135: 88-97.

10. van Strijen MJL, de Monyé W, Schiereck J, Kieft, GJ, Prins MH, et al. Single-detector helical computed tomography as the primary diagnostic test in suspected pulmonary embolism: A multicenter clinical management study of 510 patients. Ann Intern Med 2003; 138(4): 307-314.

11. Ramzi DW, Leeper KV. DVT and Pulmonary Embolism: Part II. Treatment and Prevention. American Family Physician 2004; 69(12): 2841-2848.

12. Huda W. When a pregnant patient has a suspected pulmonary embolism, what are the typical embryo doses from a chest CT and a ventilation/perfusion study? Pediate Radiol 2005;35:452-453.

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