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* Score 4 or less - PE unlikely. Consider [[D-dimer]] to rule out PE.
* Score 4 or less - PE unlikely. Consider [[D-dimer]] to rule out PE.


=== Differential Diagnosis ===
==[[Pulmonary embolism differential diagnosis|Differential Diagnosis]]==
Part of what makes the diagnosis of PE difficult is that the differential diagnosis of the clinical presentation of PE is extensive including a long list of conditions causing [[chest pain]]. Whats more, PE can accompany any of the above diagnoses.
 
* [[Anemia]]
* [[Angina pectoris]]
* [[Aortic stenosis]]
* [[Atrial fibrillation]]
* [[Cardiogenic shock]]
* [[Chronic Obstructive Pulmonary Disease]]
* [[Cor pulmonale]]
* [[Costochondritis]]
* [[Emphysema]]
* [[Herpes zoster]]
* [[Mitral stenosis]]
* [[Musculoskeletal pain]]
* [[Pleuritis]]
* [[Rib fracture]]
* [[Pericarditis]]
* [[Salicylate intoxication]]
* [[Hyperventilation]]
* [[Myocardial infarction]]
* [[Myocardial ischemia]]
* [[Myocarditis]]
* [[Bacterial pneumonia]]
* [[Community acquired pneumonia]]
* [[Pneumothorax]]
* [[Septic shock]]
* [[Distributive shock ]]
* [[Hemorrhagic shock]]
* [[Sudden cardiac death]]
* [[Syncope]]
* [[Toxic shock syndrome]]
* [[Viral pneumonia]]


==[[Pulmonary embolism history & symptoms|History & Symptoms]]==
==[[Pulmonary embolism history & symptoms|History & Symptoms]]==
Line 121: Line 89:
==[[Pulmonary embolism computed tomography|Computed Tomography]]==
==[[Pulmonary embolism computed tomography|Computed Tomography]]==


==[[Pulmonary embolism ventilation/perfusion scan|Ventilation/perfusion scan]]==
==[[Pulmonary embolism ventilation/perfusion scan|Ventilation/Perfusion scan]]==
 
''[[Ventilation/perfusion scan]]'' (or ''V/Q scan'' or ''lung [[scintigraphy]]''), which shows that some areas of the lung are being ventilated but not perfused with blood (due to obstruction by a clot). This type of examination is used less often because of the more widespread availability of CT technology, however, it may be useful in patients who have an allergy to [[iodinated contrast]] or in [[pregnancy]] due to lower radiation exposure than CT. * The ventilation/perfusion ratio (V/Q) Scan: The PIOPED data suggests that normal perfusion scans are almost never associated with recurrent pulmonary embolism, even if anticoagulation is withheld.
:* High-prob scans, however only identified 41% of patients with PE.
:* In the setting of a high pre-test probability, a high-prob scan revealed PE in 95% of cases.
:* Unfortunately, 41% of all scans in PIOPED were interpreted as intermediate, and an additional 16% were interpreted as low-prob.
:** Upon angiography, however, 30 and 14% of these patients respectively were found to have PE.
:** Based on these numbers, there has been a huge movement to abolish the low-prob, and intermediate-prob categories, and have readings either be high-prob, normal, or non-diagnostic.
:* It should also be realized that the false-positive rate for high-prob scans was 14%, and that 72% of patients in PIOPED had a clinical – scan combination that required further investigation.
* It has been suggested by some authors that patients with an intermediate pre-test probability of PE a + venous ultrasound would provide the same justification for anticoagulation as would a confirmed PE.
* Spiral CT scanning is now a standard modality to non-invasively diagnose PE.
*:* Initial studies reported sensitivities for diagnosing emboli to the segmental level (4th order branch) as high as 98%, however subsequent studies have found sensitivities to be lower.
*:* Obviously, the sensitivity is higher with more proximal clot.
*:* Although smaller clot, in the subsegmental arteries, is certainly not as physiologically important as the larger, more proximal clot, they may be important predictors of future, larger clots.
*:* The study by Mayo et.al. concludes that the sensitivity and specificity of CT angio are higher than that of V/Q scans, as is the inter-observer agreement.
*:*:* They recommend getting a CT angio as the next test following an indeterminate V/Q    scan, however caution that if the pre-test probability is ‘sufficiently high’ a standard angiogram should still be obtained after a negative CT angio.
* van Erkel et.al. performed a cost-effective analysis using spiral CT angio for the diagnosis of PE.
*:* The use of CT angio in a diagnostic algorithm was by far and away a more cost-effective strategy.
*:* If the sensitivity of CT angio was < 85%, conventional angiography was associated with a lower mortality, but still remained a more expensive strategy.


==[[Pulmonary embolism echocardiography or ultrasound|Echocardiography or Ultrasound]]==
==[[Pulmonary embolism echocardiography or ultrasound|Echocardiography or Ultrasound]]==

Revision as of 17:02, 20 July 2011

Pulmonary embolism
ICD-10 I26
ICD-9 415.1
DiseasesDB 10956
MedlinePlus 000132

Pulmonary Embolism Microchapters

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Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Pulmonary Embolism from other Diseases

Epidemiology and Demographics

Risk Factors

Triggers

Natural History, Complications and Prognosis

Diagnosis

Diagnostic criteria

Assessment of Clinical Probability and Risk Scores

Pulmonary Embolism Assessment of Probability of Subsequent VTE and Risk Scores

History and Symptoms

Physical Examination

Laboratory Findings

Arterial Blood Gas Analysis

D-dimer

Biomarkers

Electrocardiogram

Chest X Ray

Ventilation/Perfusion Scan

Echocardiography

Compression Ultrasonography

CT

MRI

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Risk calculators and risk factors for Pulmonary embolism

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

Synonyms and Associated Terms: PE

Pulmonary embolism (PE) is a common illness that can cause death and significant disability. PE occurs when there is an acute obstruction of the pulmonary artery (or one of its branches). Most often this is due to a venous thrombus (blood clot from a vein), which has been dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs. This process is termed thromboembolism.

Patients present with a wide array of symptoms and signs. These may include difficulty breathing, pain in the chest during breathing, and in more severe cases collapse, circulatory instability and sudden death. PE treatment requires rapid and accurate risk stratification before haemodynamic decompensation and the development of cardiogenic shock. Therapeutic application most often consists of an anticoagulant medication, such as heparin and warfarin, and rarely (in severe cases) with thrombolysis or surgery. In other, rarer forms of pulmonary embolism, material other than a blood clot is responsible; this may include fat or bone (usually in association with significant trauma), air (often when diving), clumped tumor cells, and amniotic fluid (affecting mothers during childbirth).

Epidemiology and Demographics

Risk factors

Pathophysiology

Natural History, Complications & Prognosis

Diagnosis

The diagnosis of PE is based primarily on the clinical evaluation combined with diagnostic modalities such as spiral CT, V/Q scan, use of the D-dimer and lower extremity ultrasound.

Pretest Probability

In spite of all of nonspecific clinical and lab findings, it has been shown that clinicians are actually fairly good at assigning meaningful clinical probabilities for PE.

  • In PIOPED, 67% of the patients labeled as having a high clinical probability (>80% likelihood) had PE, as compared with only 9% of those give a low clinical probability (<20% likelihood).
  • Unfortunately, the majority of patients (64%) were assigned an intermediate clinical probability (20 – 80% likelihood), reinforcing the fact that a clinical diagnosis can be difficult.

High Pretest Probability

Many authors, reserve the term high pretest probability for those patients with a clinical presentation consistent with PE, in whom an alternative diagnosis is not apparent (e.g. pneumonia) and who have known risk factors for venous thromboembolism (VTE).

Low Pretest Probability

Low pretest probability patients include those patients with an alternative diagnosis to explain the clinical findings or those without risk factors.

Intermediate Pretest Probability

Intermediate probability patients include those patients not fitting either high or low pretest probability definitions.

Predicting the Risk of Pulmonary Embolism

The decision to do medical imaging is usually based on clinical grounds, i.e. the medical history, symptoms and findings on physical examination.

Development of the Wells score

The most commonly used method to predict clinical probability, the Wells score, is clinical prediction rule, whose use is complicated by multiple versions being available. In 1995, Wells et al initially developed a prediction rule (based on a literature search) to predict the likelihood of PE, based on clinical criteria.[1] The prediction rule was revised in 1998[2] This prediction rule was further revised when simplified during a validation by Wells et al in 2000.[3] In the 2000 publication, Wells proposed two different scoring systems using cutoffs or 2 or 4 with the same prediction rule.[3] In 2001, Wells published results using the more conservative cutoff of 2 to create three categories.[4] An additional version, the "modified extended version", using the more recent cutoff of 2 but including findings from Wells's initial studies[1][2] were proposed.[5] Most recently, a further study reverted to Wells's earlier use of a cutoff of 4 points[3] to create only two categories.[6]

There are additional prediction rules for PE, such as the Geneva rule. More importantly, the use of any rule is associated with reduction in recurrent thromboembolism.[7]

Wells score

The Wells score:[8]

  • clinically suspected DVT - 3.0 points
  • alternative diagnosis is less likely than PE - 3.0 points
  • tachycardia - 1.5 points
  • immobilization/surgery in previous four weeks - 1.5 points
  • history of DVT or PE - 1.5 points
  • hemoptysis - 1.0 points
  • malignancy (treatment for within 6 months, palliative) - 1.0 points
Interpretation of the Wells score

Traditional interpretation[3][4]

  • Score >6.0 - High (probability 59% based on pooled data[9])
  • Score 2.0 to 6.0 - Moderate (probability 29% based on pooled data[9])
  • Score <2.0 - Low (probability 15% based on pooled data[9])

Alternate interpretation[3][6]

  • Score > 4 - PE likely. Consider diagnostic imaging.
  • Score 4 or less - PE unlikely. Consider D-dimer to rule out PE.

Differential Diagnosis

History & Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Pulmonary Angiography

Computed Tomography

Ventilation/Perfusion scan

Echocardiography or Ultrasound

Chest Xray

Magnetic Resonance Imaging

Low Probablitity Diagnostic Tests and non-Diagnostic Tests

Tests that are frequently done that are not sensitive for PE, but can be diagnostic.


  • Ultrasonography of the legs, also known as leg doppler, in search of deep venous thrombosis (DVT). The presence of DVT, as shown on ultrasonography of the legs, is in itself enough to warrant anticoagulation, without requiring the V/Q or spiral CT scans (because of the strong association between DVT and PE). This may be valid approach in pregnancy, in which the other modalities would increase the risk of birth defects in the unborn child. However, a negative scan does not rule out PE, and low-radiation dose scanning may be required if the mother is deemed at high risk of having pulmonary embolism.

Combining tests into algorithms

Recent recommendations for a diagnostic algorithm have been published by the PIOPED investigators; however, these recommendations do not reflect research using 64 slice MDCT.[9] These investigators recommended:

  • Low clinical probability. If negative D-dimer, PE is excluded. If positive D-dimer, obtain MDCT and based treatment on results.
  • Moderate clinical probability. If negative D-dimer, PE is excluded. However, the authors were not concerned that a negative MDCT with negative D-dimer in this setting has an 5% probability of being false. Presumably, the 5% error rate will fall as 64 slice MDCT is more commonly used. If positive D-dimer, obtain MDCT and based treatment on results.
  • High clinical probability. Proceed to MDCT. If positive, treat, if negative, addition tests are needed to exclude PE.

Medical Therapy

Surgery

Prognosis

Mortality from untreated PE is said to be 26%. This figure comes from a trial published in 1960 by Barrit and Jordan[10] which compared anticoagulation against placebo for the management of PE. Barritt and Jordan performed their study in the Bristol Royal Infirmary in 1957. This study is the only placebo controlled trial ever to examine the place of anticoagulants in the treatment of PE, the results of which were so convincing that the trial has never been repeated as to do so would be considered unethical. That said, the reported mortality rate of 26% in the placebo group is probably an overstatement, given that the technology of the day may have detected only severe PEs.

Prognosis depends on the amount of lung that is affected and on the co-existence of other medical conditions; chronic embolisation to the lung can lead to pulmonary hypertension. There is controversy over whether or not small subsegmental PEs need to be treated at all[11] and some evidence exists that patients with subsegmental PEs may do well without treatment.[12][13]

Predicting mortality

The PESI and Geneva prediction rules can estimate mortality and so may guide selection of patients who can be considered for outpatient therapy.[14]

Right ventricular dysfunction on echocardiography and higher than normal concentrations of troponin identify high risk patients who might need escalation of therapy with thrombolysis or embolectomy even if the blood pressure is normal on presentation.

Evaluation for underlying causes for recurrence

After a first PE, the search for secondary causes is usually brief. Only when a second PE occurs, and especially when this happens while still under anticoagulant therapy, a further search for underlying conditions is undertaken. This will include testing ("thrombophilia screen") for Factor V Leiden mutation, antiphospholipid antibodies, protein C and S and antithrombin levels, and later prothrombin mutation, MTHFR mutation, Factor VIII concentration and rarer inherited coagulation abnormalities.

For prevention of recurrences, when patients are admitted to medical wards or when patients undergo surgery, their physicians should prescribe prophylactic measures to prevent PE. After hospital discharge, prophylaxis should continue for about a month for patients at high risk of thromboembolism.

References

  1. 1.0 1.1 Wells PS, Hirsh J, Anderson DR, Lensing AW, Foster G, Kearon C, Weitz J, D'Ovidio R, Cogo A, Prandoni P (1995). "Accuracy of clinical assessment of deep-vein thrombosis". Lancet. 345 (8961): 1326–30. doi:doi:10.1016/S0140-6736(95)92535-X Check |doi= value (help). PMID 7752753.
  2. 2.0 2.1 Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J (1998). "Use of a clinical model for safe management of patients with suspected pulmonary embolism". Ann Intern Med. 129 (12): 997–1005. PMID 9867786.
  3. 3.0 3.1 3.2 3.3 3.4 Wells P, Anderson D, Rodger M, Ginsberg J, Kearon C, Gent M, Turpie A, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J (2000). "Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer". Thromb Haemost. 83 (3): 416–20. PMID 10744147.
  4. 4.0 4.1 Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G, Ward J, Kovacs MJ (2001). "Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer". Ann Intern Med. 135 (2): 98–107. PMID 11453709.
  5. Sanson BJ, Lijmer JG, Mac Gillavry MR, Turkstra F, Prins MH, Büller HR (2000). "Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group". Thromb. Haemost. 83 (2): 199–203. PMID 10739372.
  6. 6.0 6.1 van Belle A, Büller H, Huisman M, Huisman P, Kaasjager K, Kamphuisen P, Kramer M, Kruip M, Kwakkel-van Erp J, Leebeek F, Nijkeuter M, Prins M, Sohne M, Tick L (2006). "Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography". JAMA. 295 (2): 172–9. doi:10.1001/jama.295.2.172. PMID 16403929.
  7. Roy PM, Meyer G, Vielle B, Le Gall C, Verschuren F, Carpentier F, Leveau P, Furber A (2006). "Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism". Ann. Intern. Med. 144 (3): 157–64. PMID 16461959.
  8. Neff MJ (2003). "ACEP releases clinical policy on evaluation and management of pulmonary embolism". American family physician. 68 (4): 759–60. PMID 12952389.
  9. 9.0 9.1 9.2 9.3 Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, Sos TA, Quinn DA, Leeper KV, Hull RD, Hales CA, Gottschalk A, Goodman LR, Fowler SE, Buckley JD (2007). "Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II Investigators". Radiology. 242 (1): 15–21. doi:10.1148/radiol.2421060971. PMID 17185658.
  10. "Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial". Lancet. 1: 1309&ndash, 1312. 1960. PMID 13797091. Text " Barritt DW, Jorden SC " ignored (help)
  11. Le Gal G, Righini M, Parent F, van Strijen M, Couturaud F (2006). "Diagnosis and management of subsegmental pulmonary embolism". J Thromb Haemost. 4 (4): 724–31. PMID 16634736.
  12. Perrier A, Bounameaux H (2006). "Accuracy or outcome in suspected pulmonary embolism". N Engl J Med. 354 (22): 2383–5. PMID 16738276.
  13. Stein P, Fowler S, Goodman L, Gottschalk A, Hales C, Hull R, Leeper K, Popovich J, Quinn D, Sos T, Sostman H, Tapson V, Wakefield T, Weg J, Woodard P (2006). "Multidetector computed tomography for acute pulmonary embolism". N Engl J Med. 354 (22): 2317–27. PMID 16738268.
  14. Jiménez D, Yusen RD, Otero R; et al. (2007). "Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy". Chest. 132 (1): 24–30. doi:10.1378/chest.06-2921. PMID 17625081.

Sources

  1. Bertucci, V., Asch, M.R., Balter, M., Prognosis in a patient with an initial normal pulmonary angiogram, Chest 1994; 105: 1257-1258.
  2. Cvitanic, O, Marino, P.L., Improved use of arterial blood gas analysis in suspected pulmonary embolism, Chest 1989; 95: 48-51.
  3. Drucker, E.A., et.al., Acute pulmonary embolism: assessment of helical CT for diagnosis, Radiology 1998; 209: 235-241.
  4. Ferrari, E., et.al., The ECG in pulmonary embolism: predictive value of negative T waves in precordial leads – 80 case reports, Chest 1997; 111: 537-543.
  5. Goldhaber, S.Z., et.al., Quantitative plasma D-dimer levels among patients undergoing pulmonary angiography for suspected pulmonary embolism, JAMA 1993; 270: 2819-2822.
  6. Goldhaber, S.Z., Pulmonary embolism, NEJM 1998; 339: 93-104.
  7. Mayo, J.R., et.al., Pulmonary embolism: prospective comparison of spiral CT with ventilation-perfusion scintigraphy, Radiology 1997; 205: 447-452.
  8. Meaney, J.F.M., et.al., Diagnosis of pulmonary embolism with magnetic resonance angiography, NEJM 1997; 336: 1422-1427.
  9. The PIOPED investigators, Value of the ventilation / perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED), JAMA 1990; 263: 2753-2759.
  10. Remy-Jardin, M., et.al., Diagnosis of pulmonary embolism with spiral CT: comparison with pulmonary angiography and scintigraphy, Radiology 1996; 200: 6999-706.
  11. Stein, P.D., et.al., Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease, Chest 1991; 100: 598-603.
  12. Stein, P.D., et.al., Arterial blood gas analysis in the assessment of suspected pulmonary embolism, Chest 1996; 109: 78-81.
  13. Thompson, B.T., Hales, C.A., Diagnostic strategies for acute pulmonary embolism, in UpToDate, September 10, 1998.
  14. Van Erkel, A.R., et.al., Spiral CT angiography for suspected pulmonary embolism: a cost-effective analysis, Radiology 1996; 201: 29-36.

Acknowledgements

The content on this page was first contributed by: Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3] and David Feller-Kopman, M.D.

List of contributors:

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