computed tomography in the diagnosis of pulmonary embolism scott m silvers, md 1 st pan american...
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Computed Tomography in the Diagnosis of Pulmonary Embolism
Scott M Silvers, MD
1st Pan American Conference
Emergency Medicine Clinical Policies
November 6 – 7, 2003
Lecture Outline
• Case
• Critical Question
• Literature Search
• Critical Literature Evaluation
• Evidence-based Recommendations
CaseMs. Smith is an active 39 yo F who presents to the ED with 1 day of
pleuritic left anterior chest pain and mild shortness of breath. She denies any cough, leg pain, leg swelling, recent surgery, history of malignancy, or history of DVT / PE in the past.
PMH: HypertensionMeds: BCP All: NKDA FH: None SH: Denies tobacco, alcohol, and drug abuse
T=37.6 HR= 115 SBP= 120/74 RR=20 SO2=93% RA
PE: Normal including heart, lungs, and extremities.
Chest X-ray: Normal
Case
• What next??– Ventilation / Perfusion scan? – Traditional pulmonary arteriography?– Computed Tomography (CT) scan?
CT PA in Diagnosing PE
Swensen SJ, et al. Outcomes after withholding anticoagulation from patients with suspected acute pulmonary embolismand negative computed tomographic findings: a cohort study. Mayo Clinic Proc. 2002;77:130-138.
Baseline Chest CT… Repeat Chest CT
Critical Question
• What is the diagnostic utility of computed tomography in pulmonary embolism (PE)?
–Types of CT imaging for PE
•Single detector pulmonary angiogaphy (PA)
•Multidetector PA
–Combined venography or ultrasound
–Negative CT outcome data
Literature Search
• Medline January 1992 – Present• Keywords
– “Computed tomography,” “CT,” “Pulmonary embolism,” and “PE”
973 papers
• Limits– Human subjects, clinical trials, meta-analyses 34
Literature Search
• Reviews and clinical policies – 2000 – present (references crosschecked)
Definitions for Clarity
• CT-PA = CT with pulmonary angiography
• Arteriography = Traditional pulmonary angiography
What about single-detector CT-PAfor detecting PE?
Single-Detector CT-PA vs. Arteriography for Detecting PE
• All patients compared to arteriography
• 5 studies to date
• Weaknesses– Small sample size– Large variability of findings– Inclusion of only patients referred for
arteriography (sample bias)
Single-Detector CT-PA vs. Arteriography for Detecting PE
Study Year N DesignPE
%
Sens
%
Spec
%Comments
StudyGrade
Remy-Jardin et al
1992 42 Prospective 86 100 95•Excluded inconclusive CTs
3
Blum et al 1994 10 Prospective 70 100 100 •Very small sample 3
Goodman et al
1995 20 Prospective 55 64 89•Intermediate VQ only
•Excluded if + u/s3
Remy-Jardin et al
1996 75 Prospective 57 91 78•Thoracic radiologists
•Only those referred for arteriography
2
Drucker et al
1998 47 Prospective 32 57* 89*
•Thoracic radiologists
•Only those referred for arteriography
2
* = Pooled data
Single-Detector CT-PA vs. Arteriography for Detecting PE
Study Year N DesignPE
%
Sens
%
Spec
%Comments
StudyGrade
Remy-Jardin et al
1992 42 Prospective 86 100 95•Excluded inconclusive CTs
3
Blum et al 1994 10 Prospective 70 100 100 •Very small sample 3
Goodman et al
1995 20 Prospective 55 64 89•Intermediate VQ only
•Excluded if + u/s3
Remy-Jardin et al
1996 75 Prospective 57 91 78•Thoracic radiologists
•Only those referred for arteriography
2
Drucker et al
1998 47 Prospective 32 57* 89*
•Thoracic radiologists
•Only those referred for arteriography
2
* = Pooled data
Single-Detector CT-PA vs. Arteriography for Detecting PE
• Explanations for Poor Performance– Less resolution than multi-detector CT– Digital monitor technology not available
• Image scrolling on one screen
What about multi-detector CT-PAfor detecting PE?
Multi-Detector CT-PAfor Detecting PE
• 4 studies to date
• Higher resolution (less motion artifact)
• Digital monitors with scrolling images
• Weaknesses– Studies variable in use of traditional
arteriography as “gold standard”– Large variability of findings
Multi-Detector CT-PAfor Detecting PE
Study Year N DesignPE
%
Sens
%
Spec
%Comments
StudyGrade
Qanadli et al 2000 157 Prospective 39 90 94•Consecutive patients
•All had CT & arteriography
1
Ost et al
(High Risk)2001 103 Prospective 26 81 89
•High clinical probability and Low/ intermediate VQ only
•21 lost in follow-up
3
Perrier et al 2001 299 Prospective 39 70 91•D-dimer > 500 g/L
•All 3month follow-up1
Nilsson et al 2002 90 Prospective 37 91 96•Small sample
•All had Arteriography2
Multi-Detector CT-PAfor Detecting PE
Study Year N DesignPE
%
Sens
%
Spec
%Comments
StudyGrade
Qanadli et al 2000 157 Prospective 39 90 94•Consecutive patients
•All had CT & arteriography
1
Ost et al
(High Risk)2001 103 Prospective 26 81 89
•High clinical probability and Low/ intermediate VQ only
•21 lost in follow-up
3
Perrier et al 2001 299 Prospective 39 70 91•D-dimer > 500 g/L
•All 3month follow-up1
Nilsson et al 2002 90 Prospective 37 91 96•Small sample
•All had Arteriography2
What about CT-PA with Delayed Venography for Detecting PE?
CT Venogram
Loud PA et al. Deep venous thrombosis with suspected pulmonary embolism: detection with combined CT venography and pulmonary angiography. Radiology. 2001;219:498-502.
CT Pulmonary Angiogram with Delayed Venography for Detecting PE
Typical Study Methodology– Consecutive patients with concern for PE– PE = Positive CT PA OR Positive CT venogram
– Evaluate benefit of added CT venography
Conclusions– CT venography diagnoses an additional 13 – 27%
more pulmonary embolism than CT PA alone
CT Pulmonary Angiogram with Delayed Venography for Detecting PE
Study Year N Design
CT PA or Venogram
(# PE)
Venogram
And
CT PA
CommentsStudyGrade
Loud et al
2000 71 Prospective 26 (37%) 7 (27%) •Venogram vs u/s 2
Coche et al
2000 65 Prospective 25 (38%) 3 (12%) •Small sample 2
Cham et al
2000 541 Prospective107 (20
%)16 (15%) •Venogram vs u/s 1
Loud et al
2001 650 Prospective 116 (18%) 31 (27%) •Venogram vs u/s 1
Au et al
2001 50 Prospective 14 (28%) 2 (14%) •Small sample 2
Walsh et al
2002 96 Prospective 39 (41%) 5 (13%) •Small sample 2
+ +
-
CT Pulmonary Angiogram with Delayed Venography for Detecting PE
Study Year N Design
CT PA or Venogram
(# PE)
Venogram
And
CT PA
CommentsStudyGrade
Loud et al
2000 71 Prospective 26 (37%) 7 (27%) •Venogram vs u/s 2
Coche et al
2000 65 Prospective 25 (38%) 3 (12%) •Small sample 2
Cham et al
2000 541 Prospective107 (20
%)16 (15%) •Venogram vs u/s 1
Loud et al
2001 650 Prospective 116 (18%) 31 (27%) •Venogram vs u/s 1
Au et al
2001 50 Prospective 14 (28%) 2 (14%) •Small sample 2
Walsh et al
2002 96 Prospective 39 (41%) 5 (13%) •Small sample 2
+ +
-
Is CT venography comparable to lower extremity ultrasound?
Yes.
Sensitivity of CT Delayed Venography for Detecting DVT
Study Year NPositive
CT Venogram
SENSITIVITY:
CT Venography vs. Bilateral
Lower Extremity Ultrasound
Study Grade
Loud et al 1999 71 19 100 % * 2
Garg et al 2000 68 7 100 % 2
Cham et al 2000 541 45 100 % 1
Coche et al 2001 65 16 100 % 2
Loud et al 2001 650 89 97 % * 1
Au et al 2001 50 8 100 % 2
* = CT Venography detected DVT that bilateral lower extremity ultrasound missed
Outcome Studies?
Outcome Studies of CT-PA alone for Detecting PE
• 6 studies to date
• All with significant weaknesses– Excluded patients with other positive testing
(Selection Bias)• D-dimer
• Lower extremity ultrasound
– Adequacy of follow-up period (3 mos – 1 yr)– Lose patients in follow-up
Outcome Studies of CT-PA Alone for Detecting PE
Study Year N Design Comments Grade
Ost et al2001 103 Prospective
•6 month follow up•23 (32%) patients with negative CT died •2 had autopsies (both negative)
3
Perrier et al 2001 299 Prospective•3 month follow up •Excluded abnormal d-dimers (38%)
3
Goodman
et al2000 1,015 Prospective
•3 month follow up•20% lost to follow up
3
Gottsäter et al 2001 215Retrospective
Cohort
•3 month follow up •16 died. 6 autopsies - 3 (50%) proven PEs
3
Swensen et al 2002 993Retrospective
cohort
•3 month follow up•118 (12%) died, 34 autopsies – 3 (9%) PEs •17 pts excluded for positive LE ultrasound
3
Tillie-Leblond et al
2002 46 Prospective
•3 months, 6 months, and 1 year follow up•3 (6.5%) PE during follow up (all fatal)•Excluded if other positive imaging for clot
3
Outcome Studies of CT PA with Delayed Venography for Detecting PE
None
Outcome Studies of CT PA with Bilateral Lower Extremity
Ultrasound for Detecting PE
• 2 studies to date
Outcome After a Negative CT PA with Bilateral Lower Extremity Ultrasound
Van Strijen et al (2003; “ANTELOPE” Study Group)
Van Strijen et al. Ann Int Med. 2003;138:307-315.
• Prospective, Single-detector CT• 510 Consecutive in/outpatients clinically suspected to have PE• 246 with negative CT PA & bilateral lower extremity ultrasound• 3 month follow up (100% capture)
– 3 patients returned with symptoms concerning for PE– CT PA positive in 1 (0.4% {95% CI 0.0 – 2.2%})
• Weaknesses– Followed for only 3 months
• Study Grade = 2
Outcome After a Negative CT PA with Bilateral Lower Extremity Ultrasound
Musset et al (2002)
Musset et al. Lancet. 2002;360:1914 -1920.
• Prospective, multi-detector CT• 1,041 consecutive in/outpatients suspected of having PE• 527 Low and intermediate risk patients had negative studies• 507 were not anticoagulated (others e.g. ACS)• 3 month follow up (99% capture)
– 9 (1.8 %) developed PE Of 76 “high risk” patients, 5 (5.3%) had PE
• Weaknesses– Followed for only 3 months
• Study Grade = 2
Evidenced-based RecommendationsFor CT scanning in PE
Level A Recommendations• None specified
Evidenced-based RecommendationsFor CT scanning in PE
Level B Recommendations
• Low and intermediate risk patients for pulmonary embolism may be presumed not to have pulmonary embolism following a negative CT pulmonary angiogram and bilateral lower extremity ultrasound .
• Low and intermediate risk patients for pulmonary embolism with a negative CT pulmonary angiogram and negative CT venography of the abdomen and lower extremities may be presumed not to have pulmonary embolism.
Evidenced-based RecommendationsFor CT scanning in PE
Level C Recommendations
• CT with pulmonary angiogram alone may be considered as an alternative diagnostic test to ventilation-perfusion imaging and traditional arteriography in the initial evaluation of a patient with possible pulmonary embolism.
• Consider further screening after a negative CT pulmonary angiogram alone among patients with possible pulmonary embolism.
Key References• Swensen SJ, et al. Outcomes after withholding anticoagulation from patients with
suspected acute pulmonary embolism and negative computed tomographic findings: a cohort study. Mayo Clinic Proc. 2002;77:130-138.
• Remy-Jardin M, et al. Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique--comparison with pulmonary angiography.Radiology. 1992 Nov;185(2):381-7.
• Blum AG, et al. Spiral-computed tomography versus pulmonary angiography in the diagnosis of acute massive pulmonary embolism. Am J Cardiol. 1994 Jul 1;74(1):96-8.
• Goodman et al. Detection of pulmonary embolism in patients with unresolved clinical and scintigraphic diagnosis: helical CT versus angiography. Am J Roentgenol. 1995;164:1369-1374.
• Remy-Jardin M, et al. Diagnosis of pulmonary embolism with spiral CT: comparison with pulmonary angiography and scintigraphy. Radiology. 1996;200(3):699-706.
• Drucker N, et al. Acute pulmonary embolism: assessment of helical CT for diagnosis. Radiology. 1998;209:235-241.
• Qanadli SD, et al. Pulmonary embolism detection: prospective evaluation of dual-section helical CT versus selective pulmonary arteriography in 157 patients. Radiology. 2000;217:447-455.
Key References• Ost D, et al. The negative predictive value of spiral computed tomography for the diagnosis of
pulmonary embolism in patients with nondiagnostic ventilation-perfusion scans. Am J Med. 2001;110:16-21.
• Perrier A, et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Ann Int Med. 2001;135:88-97.
• Nilsson T, et al. A comparison of spiral computed tomography and latex agglutination d-dimer assay in acute pulmonary embolism using pulmonary arteriography as gold standard. Scand Cardiovasc J. 2002;36(6):373-7.
• Loud PA, et al. Deep venous thrombosis with suspected pulmonary embolism: detection with combined CT venography and pulmonary angiography. Radiology. 2001;219:498-502.
• Loud PA, et al. Combined CT venography and pulmonary angiography in suspected thromboembolic disease: diagnostic accuracy for deep venous evaluation. Am J Roentgenol. 2000;174:61-65.
• Cham MD, et al. Deep venous thrombosis: detection by using indirect CT venography. Radiology. 2000;216:744-751.
• Coche EE, et al. Using dual-detector helical CT angiography to detect deep venous thrombosis in patients with suspicion of pulmonary embolism: diagnostic value and additional findings. Amer J Roentgenol. 2001;176:1035-1039.
• Au V WK, et al. Computed tomography pulmonary angiography with pelvic venography in the evaluation of thrombo-embolic disease. Australasian Radiology. 2001;45:141-145.
Key References• Walsh G, and Redmond S. Does addition of CT pelvic venography to CT pulmonary
angiography protocols contribute to the diagnosis of thromboembolic disease? Clinical Radiology. 2002;57:462-465.
• Garg K, et al. Thromboembolic disease: comparison of combined CT pulmonary angiography and venography with bilateral leg sonography in 70 patients. Amer J Roentgenol. 2000;175:997-1001.
• Goodman LR, et al. Subsequent pulmonary embolism: risk after a negative helical CT pulmonary angiogram – prospective comparison with scintigraphy. Radiology. 2000;215:535-542.
• Gottsäter A, et al. Clinically suspected pulmonary embolism: is it safe to withhold anticoagulation after a negative spiral CT? Eur Radiol. 2001;11:65-72.
• Tillie-Lebond I, et al. Risk of pulmonary embolism after a negative spiral CT angiogram in patients with pulmonary disease: 1-year clinical follow-up study. Radiology. 2002;223:461-467. Musset et al. Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study. Lancet. 2002;360:1914 -1920.
• Van Strijen 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 Int Med. 2003;138:307-315
The End