Briefly outline the role of each of the following in the diagnosis of pulmonary embolism in the critically ill:

a) Echocardiography

b) CT pulmonary angiogram (CTPA)

c) Serum troponin

d) D-dimer levels

[Click here to toggle visibility of the answers]

College Answer

Echo
 Bedside test, rapid.
 Avoids transport, radiation exposure, IV contrast.
 Only 30-40% with PE have suggestive changes. Changes more likely if massive.
 Signs of right heart failure with shock and known PE may be an indication for thrombectomy / thrombolysis.

CTPA
 Spiral CT scan with IV contrast.
 Ability to also detect alternative pulmonary abnormalities.
 Issues of transport, radiation exposure, IV contrast (versus bedside tests (e.g. leg duplex U/S, ECHO) and/or empiric anticoagulation).
 PIOPED II – suggested that CTPA requires concomitanTrt pre-test probability assessment (Wells) to be effective tool in diagnosing or excluding. Positive and negative predictive values differed significantly at different pre-test probabilities.
 Positive predictive value varies with extent of PE and pre-test probability – v good (97%) with main or lobar, falling with smaller; v good with high pre-test probability (96%), falling with lower (NEJM 2006).
 More recent studies with newer generation scanners suggest CTPA better at excluding PE than in PIOPED II - if good quality negative CTPA in an experienced centre, representation with thromboembolism is 1 – 2% at 3 months. In high risk patients, closer to 5TTE%. (J Thromb Haemost 2009).

Troponin
 Not useful for diagnosis of PE.
 Elevated in 30 – 50% with moderate/large PE.
 Presumably from acute RV strain/overload.
 Associated with poorer prognosis.

D-dimer
 Degradation product of cross-linked fibrin.
 Detected in serum (ELISA or agglutination assay).
 Multitude of causes of raised D-dimer other than PE.
 Good sensitivity.
 Good negative predicative value – increased further if use clinical pre-test probability (e.g. Wells).
 Poor specificity and positive predictive value.
 Main role is to exclude PE if low pre-test probability and negative D-dimer.
 No use in the critically ill population as elevated in elderly, post-op, infection, trauma.

Examiners' comments: Candidates did not answer the question as asked.

Discussion

It was not a "compare and contrast" question, but judging by the examiner's comments it was treated as one by many candidates.  However, the college answer to this question still discusses the advantages and disadvantages of these investigations. So, here is a "compare and contrast" sort of table, which incorporates both the model college answer and the 2014 ESC guidelines.

Investigations for Pulmonary Embolism
Test Rationale and advantages Limitations and disadvantages
History and clinical examination
  • Cheap and rapidly available
  • Screening for predisposing factors and associated features is effective in building pre-test probability (Well's rule or the Geneva score)
  • Clinical features of PE (eg. chest pain, dyspnoea, tachycardia) are highly non-specific.
ECG features of RV strain
  • These are
    - inverted T waves in V1-V4
    - S1Q3T3 pattern
    - RBBB
  • Only present in very severe cases
  • Frequently, sinus tachycardia is the only ECG feature
TTE
  • Rapid bedside test
  • No contrast or radiation exposure
  • May reveal RV dysfunction, which would be an indication for thrombolysis
  • Interpreter-dependent accuracy
  • Only 30-40% with PE have suggestive changes; thus a negative result does not exclude PE
CTPA
  • Rapid and easily available
  • May reveal alternative chest pathology
  • New scanners are better at excluding PE
  • The college mentions PIOPED II (2006):
    • sensitivity of 83%
    • specificity of 96%
  • Both contrast and radiation exposure
  • Risk of transport to and from the scanner
  • What if you find a small sub-segmental PE? What clinical significance does this finding have?
Troponin
  • New high-sensitivity tests are good at excluding RV injury
  • Troponin is elevated in 30 – 50% with moderate/large PE.
  • A raised troponin in PE is associated with a poorer prognosis.
  • Poor specificity: will be elevated in a number of situations apart from PE.
D-dimer
  • Good sensitivity: a negative D-dimer excludes PE.
  • Good way of excluding PE in well patientsd with a low pre-test probability
  • Three-month thromboembolic risk was less than 1% in patients left untreated
    on the basis of a negative test result.
  • Poor specificity: will be elevated in a number of situations apart from PE.
  • Critically ill populations invariably have an elevated D-dimer.
  • NNT (number needed to test) is 3 in the ED, but over 10 in other scenarios
Lung scintigraphy (V/Q scan)
  • IV injection of Tc99m-labelled macroaggregated albumin particles are used in the perfusion scan
  • Xe133 gas is then used as a ventilation scan.
  • Total radiation exposure (1.1mSv) is much lower than in a CTPA
  •  it is safe to withhold anticoagulant  therapy in patients with a normal perfusion scan.
  • Not available everywhere
  • Will not detect small PEs
  • Not available for urgent pre-thrombolysis confirmation of PE
     
     

References

References

Oh's Intensive Care manual: Chapter 34   (pp. 392) Pulmonary  embolism by Andrew  R  Davies  and  David  V  Pilcher

Anderson, Frederick A., and Frederick A. Spencer. "Risk factors for venous thromboembolism." Circulation 107.23 suppl 1 (2003): I-9.

Konstantinides, Stavros V., et al. "2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism." European Heart Journal (2014): ehu283.

Kucher, Nils, et al. "Massive pulmonary embolism." Circulation 113.4 (2006): 577-582.

Jerjes-Sanchez, Carlos, et al. "Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomized controlled trial." Journal of thrombosis and thrombolysis 2.3 (1995): 227-229.

Kucher, Nils, and Samuel Z. Goldhaber. "Management of massive pulmonary embolism." Circulation 112.2 (2005): e28-e32.

Wan, Susan, et al. "Thrombolysis compared with heparin for the initial treatment of pulmonary embolism a meta-analysis of the randomized controlled trials." Circulation 110.6 (2004): 744-749.

Kasper, Wolfgang, et al. "Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry." Journal of the American College of Cardiology 30.5 (1997): 1165-1171.

Kline, J. A., et al. "Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double‐blind, placebo‐controlled randomized trial." Journal of Thrombosis and Haemostasis 12.4 (2014): 459-468.

Sharifi, Mohsen, et al. "Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” Trial)." The American journal of cardiology 111.2 (2013): 273-277.

Stein, Paul D., et al. "Multidetector computed tomography for acute pulmonary embolism." New England Journal of Medicine 354.22 (2006): 2317-2327.