Pulmonary%20thromboembolism Diagnosis

• Clinically unstable patients may have massive pulmonary embolism (PE)
• Thrombolytic therapy should be considered

Clinical Pretest Probability of Pulmonary Embolism (CPTP)

• Evaluating the likelihood of pulmonary embolism (PE) in an individual patient according to the clinical presentation is of utmost importance in the interpretation of diagnostic test results & the selection of an appropriate diagnostic strategy
• A reasonable clinical suspicion is required to avoid missing the diagnosis of PE
• Clinical evaluation allows patients to be classified into probability categories corresponding to an increasing prevalence of PE
• Clinical probability may be estimated implicitly by clinical judgment or explicitly by a validated prediction rule
• All patients w/ possible PE should have clinical probability assessed & documented
• Patients should also be evaluated for risk factors for venous thromboembolism (VTE)
  

Prediction Rule vs Clinical Judgment

• To identify a patient w/ a high likelihood of PE, prediction rules appear to be more accurate than clinical judgment
• Clinical judgment is accurate to discern whether patient is of low likelihood of PE
  
  • Patients that have low clinical probability of PE, no lower limb deep vein thrombosis (DVT) & nondiagnostic lung scan have low risk of PE
    

Estimation of Pretest Probability of PE

• Methods: Wells, Wicki, Kline, revised Geneva score
  
  • Wells method is the most frequently used clinical prediction rule
• In any of the methods used, the proportion of patients w/ PE is around 10% in the category of low probability, 30% in moderate probability, & 65% in high probability
• Clinical evaluation allows patients to be classified into probability categories corresponding to an increasing prevalence of PE
  

Wells (Canada) Method

• Requires that the patient have clinical features suggestive of PE (eg breathlessness, &/or tachypnea w/ or without pleuritic chest pain, &/or hemoptysis)
• Along w/ 2 other features: 
  
  • Absence of another reasonable clinical explanation or
  • Presence of a major risk factor
• If both are true then the probability is high
• If only one of the above is true then the probability is intermediate
• If neither is true then the probability is low

Pulmonary Embolism Rule-Out Criteria (PERC)

• Helps exclude patients at very low risk for PE
• Studies show that PERC validation done prior to D-dimer testing is 100% sensitive
• Presence of any of the following indicates a positive PERC
  
  • Age > 49 years old
  • Pulse rate >99 bpm
  • Pulse oximetry <95% at room air
  • Hemoptysis
  • Patient on exogenous Estrogen therapy
  • Clinical history of venous thromboembolism
  • Previously intubated due to surgery or trauma or hospitalization within the last 4 weeks
  • Unilateral leg (calf) swelling

Prognostic Risk Assessment

• Assessed using Pulmonary Embolism Severity Index (PESI) & simplified PESI (sPESI), Hestia criteria, cardiacmarkers (eg cardiac troponin I, natriuretic peptide), & imaging tests
• High risk: Hemodynamic instability (eg shock, persistent arterial hypotension), PESI class III-V or sPESI ≥1, presence of signs of RV dysfunction upon imaging tests, & presence of cardiac markers
• Intermediate risk: PESI class III-V or sPESI ≥1, presence of signs of RV dysfunction upon imaging tests, &/or presence of cardiac markers
  • In intermediate-high risk patients, both cardiac markers & imaging results are positive for abnormalities
  • Either cardiac markers or signs of RV dysfunction are present in patients w/ intermediate-low risk
• Low risk: No signs of RV dysfunction on imaging tests (eg echocardiography, CT angiogram) & negative cardiac markers

Massive PE

• In patients who are too unstable for lung imaging, right ventricle (RV) dysfunction can usually be found at the bedside
  
  • Left parasternal heave, distended jugular veins & systolic murmur of tricuspid regurgitations that increases w/ inspiration
  • ECG may show new right bundle branch block, RV failure, or other evidence of RV strain (eg inverted T waves in leads V1-V4)
• The most useful initial test is echocardiography which is able to show indirect signs of acute pulmonary hypertension & RV overload if acute PE is the cause of hemodynamic compromise
• When patient has already been stabilized by supportive treatment, definite diagnosis should be determined
• CT pulmonary angiography may be used to confirm diagnosis (≥50% decreased perfusion)

• First-line diagnostic tests such as electrocardiography (ECG), chest X-ray (CXR) & arterial blood gases (ABG) are indicated to assess clinical probability of PE & general condition of patient
• Laboratory results can be normal but some abnormal findings increase the suspicion for PE

Arterial Blood Gas (ABG)

• Can show hypoxemia, hypocapnia, & widened (A-a) O₂ difference

Chest X-ray (CXR)

• May demonstrate atelectasis, pleural-based infiltrates or effusions, or engorged central pulmonary artery associated w/ a paucity of peripheral vessels

Electrocardiogram  ECG)

• Can show right axis deviation, supraventricular arrhythmia, S₁Q₃T₃ pattern or P-pulmonale

B-type Natriuretic Peptide (BNP) & Troponin

• Consider in a patient w/ substantial clot burden, abnormal echocardiogram, or clinical findings suggestive of PE
• Elevated BNP & troponin are associated w/ RV strain & increased mortality even in the absence of hemodynamic instability, especially if considering massive PE

D-Dimer

• D-dimer is a highly sensitive but a nonspecific screening test for the presence of PE
  
  • Sensitivity may be decreased if the duration of VTE manifestations is >2-3 days prior to testing, if the patient is on Heparin therapy, &/or w/ history of recent surgical procedure or trauma
  • Best used for evaluation of outpatients in the emergency department
• Recommended confirmatory test for patients w/ low pretest probability & positive for PERC
• A negative D-dimer test via any D-dimer method (simpliRed, Vidas or MDA) reliably excludes PE in patients w/ low clinical probability; such patients do not require imaging for VTE
• A negative D-dimer test using ELISA (Vidas) reliably excludes PE in patients w/ intermediate probability
• A positive D-dimer requires further evaluation to exclude PE adequately
  
  • However, raised levels of D-dimer does not confirm the presence of VTE because such levels are found in hospitalized patients, obstetrics, peripheral vascular disease, cancer & many inflammatory diseases as well as increasing age
• CV D-dimer should not be performed in those w/ high clinical probability of PE
  • Computed tomographic pulmonary angiography (CTPA) is recommended as initial test for these cases; if not available, or if patient is unstable or has contraindications, bedside echocardiography is recommended
• D-dimer is inappropriate for suspected VTE w/ recent surgery or trauma
  • These patients should proceed directly to radiologic studies (eg duplex US or CTPA)

Echocardiography

• Most useful initial test which typically shows indirect signs of acute pulmonary hypertension & RV overload if acute PE is the cause of hemodynamic changes
• If patient is unstable, thrombolytic treatment or surgery can be done based only on compatible echocardiography findings
• If patient has been stabilized, a definitive diagnosis should be pursued
  
  • Both lung scan, spiral computed tomography (sCT) & bedside transesophageal echocardiography (TEE) are usually able to confirm diagnosis
  • Normal lung scan or sCT angiogram suggests that another cause of shock should be found

Computed Tomographic Pulmonary Angiography (CTPA)

• Recommended as the initial lung imaging modality for non-massive PE
• Increasingly used as an adjunct or alternative to other imaging modalities & is superior in specificity to isotope lung scanning
• Enables direct visualization of the pulmonary emboli & may provide information about parenchymal abnormalities that might help to establish an alternative diagnosis
• More useful for patients w/ underlying cardiac & pulmonary disease
• Has a high specificity & sensitivity for central clots
• The main disadvantage of CTPA to that of conventional pulmonary angiography is that subsegmental clot is less likely to be seen
• In patients w/ a high pretest probability, negative CTPA may not be able to exclude significant pulmonary thrombi, therefore, these cases may require further investigation (refer to Section 6 - Further Work-up)
• Most experts agree that a patient, in whom CTPA shows PE, may be treated without further tests

Further Work-Up

• Recommended for patients w/ persistent signs & symptoms despite a negative CTPA & D-dimer test

Venous Duplex Ultrasonography (US)

• Most pulmonary emboli arise from the deep veins of the legs thus it is rational to search for a residual DVT in suspected PE patients
• Normal US exam of the leg veins does not rule out PE
• US studies may have false positive or may detect residual abnormalities from past VTE
  
  • Only definite positive studies under certain clinical circumstances (eg patient without history of VTE but has a high clinical probability of PE) should serve as a basis for the start of therapy
• May improve estimation of the clinical probability of PE & avoid more invasive testing in patients w/ a negative lung imaging study

Ventilation-Perfusion Lung Scanning (V/Q Scan)

• Preferred imaging study when CTPA is contraindicated
• Normal or near normal lung scans are sufficient to exclude PE, regardless of pretest probability
• Low probability scans in combination w/ a low pretest probability make probability of PE low
• High probability scans provide the predictive power to establish diagnosis in context of reasonable clinical suspicion of PE
• Presence of pulmonary vasculature occlusion of ≥50% may signify massive PE
• Further tests should be performed in all other combinations of V/Q scan result & clinical probability

Echocardiography

• Useful for rapid triage in acutely ill patients w/ suspected massive PE
  
  • Usually reliable to differentiate between illnesses that have radically different treatment compared to PE (eg AMI, pericardial tamponade, infective endocarditis, aortic dissection)
  • May suggest/reinforce clinical suspicion of PE w/ the findings of RV overload & dysfunction in the presence of Doppler signs of increased pulmonary arterial pressure
  • May also definitively confirm diagnosis of PE by visualization of proximal pulmonary arterial thrombi
• It has not been confirmed if echocardiography can identify patients who would benefit from thrombolytic therapy if they present without shock or hypotension

Magnetic Resonance Angiography (MRA)

• Appears to be promising in human & animal models
• It avoids ionizing radiation but has a poor sensitivity for subsegmental clots & limited access is likely to continue for several years

Conventional Pulmonary Angiography

• Historically considered the gold standard for the diagnosis of PE
• Limitations include: Requirement of expertise in performance & interpretation, it is invasive & there are associated risks
  
  • W/ subsegmental clot, there can be interobserver disagreement in up to 1/3 of cases
• Angiography should be reserved for patients in whom noninvasive tests remain inconclusive or are not available
• Use of pulmonary angiography may also depend on patient’s clinical status & necessity to obtain an absolute diagnosis