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Project: Ghana Emergency Medicine Collaborative
Document Title: The Emergency Department Management of Pulmonary
Embolism
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The Emergency Department
Management of Pulmonary Embolism
Rashmi U. Kothari, MD
Kalamazoo College of Medical Science
Borge...
Goals
PE is complication of venous thrombosis
  PE is very, very common
  Diagnosing only a very small % of PEs
  The c...
20 y.o Male College Student with
Hypotension & Questionable Syncope

  Found

knocking at
neighbors door
  BP=60/p P=125...
Pulmonary Embolism
3rd most common cause of death
  Most

common fatal missed diagnosis

  #2 cause of unanticipated dea...
Fatal PE in-hospital
70% misdiagnosed antemortum
70% of PE
cases
unsuspected
until autopsy

Reference: Coon: Arch Surg 197...
Mayo inpatient PE deaths
Autopsies between 1985 - 1989
  Listed

cause of death correct in only 32%
  Only 22% had a dia...
Missed PE: autopsy incidence
33 published autopsy studies
  33

studies between 1980 - 1995
  150,000 autopsies
  Fract...
Fatal PE: missed Dx by age
Dx missed in 90% of older patients

Reference: Goldhaber: Am J Med 1982; 73

10
Inpatients vs out-of-hospital
No difference in the incidence
of PE found at autopsy

Sperry: Hum Pathol 1990; 21
11
Mortality in PE
By treatment type
35%
30%
25%

35%

20%
15%
10%

9%

5%
0%

No treatment

Heparin

5%
Thrombolytics

Refer...
Mortality reduction w/ heparin
1358 medical admissions randomized
31% mortality
reduction

Reference: Halkin:Ann Intern Me...
Risk Factors for PE & DVT
 

Hypercoaguable state
–  Protein S & C def
-Anti-Thrombin III def*
–  Pregnancy
-BCP (>35 yo ...
Risk Factors for PE
Clinical Trial
(n=117)
Immobile
Surgery
Malignancy
Thrombophlebitis

Trauma
Post-Partum <3 mos.
No Ris...
Pathophysiology of PE
  Majority caused by DVT
–  15-30X more common
–  50-90% with pelvic/lower ext. clot
 
 
 

Pate...
Incidence of PE in patients with DVT
Level

No PE

Asymp. PE

Symp. PE

Total PE

40 (56.5%)

4 (6.5%)

28 (39%)

32(45.5%...
PE from calf vein DVT
Common and often fatal

References:
Moreno-Cabral Surgery 1976;80
Havig: Acta Chir Scand 1977;478
Ko...
Autopsy source of PE

Reference: Havig: Acta Chir Scand 1977;478

19
Chronic pulmonary HTN
In 70% of those with recurrent PE

Reference: Riedel: Chest 1982;81

20
512 autopsy cases
With isolated upper-extremity DVT
Responsible for
massive fatal PE

10%

90%

Other

Reference: Diebold:...
Catheter-associated DVT
One-year autopsy study of PE
  Autopsies

with catheter DVT at one hospital
  10 fatalities from...
PE from catheter-related DVT
20 cases of upper-extremity DVT
associated with indwelling catheters

  6/20

had PE
  1 di...
Pathophysiology (cont)
  Obstructs

pulmonary vasculature
  Increased physiologic deadspace in lung
  Increases PA & RV...
Clinical Presentation
Symptom

Clinical Trials1 Autopsy2

Dyspnea

84%

59%

Pleuritic Chest Pain

74%

8%

Hemoptysis

27...
Signs of PE
Sign
Tachypnea >16
Tachypnea >20
Tachycardia >100

Clinical Trials

Autopsy*

92%

66%

70%

NA

30%

54%

Fev...
PE & asymptomatic DVT
2/3 with PE have no DVT symptoms

asymptomatic DVT
in patients with PE
Reference: Walsh: J Obstet Gy...
Clinical Dx of DVT unreliable
50% false positives and negatives

In asymptomatic
patients and in
patients with
pain, tende...
ED Evaluation of PE
Prospective, all pleuritic chest pain (n=173)
  EKG, CXR, V/Q,
  Angio (low, intermed., & high prob ...
Laboratory Tests
  CXR
  EKG
  ABG
  D-Dimer

30
Chest X-ray
Non-specific & insensitive
  Findings:
 

–  Normal
–  Elevated hemi-diaphram
–  Focal infiltrate (w/in 3 da...
Electrocardiogram
  Poor

sensitivity & specificity
  Findings:
–  Tachycardia
–  Non-specific ST-T wave changes
–  Rt o...
PO2 in Patients with & without PE

Percent of Patients

(no prior history of Cardiac or Pulmonary disease)

Room Air PO2 (...
Arterial Blood Oxygen
  0%

predictive value
  17% PO2 > 80 mmHg
  5% PO2 > 100 mmHg

34
ABG does not predict PE
(120 possible PE, 54 with PE)

PO2

Incidence of PE Incidence of PE
below level
above level

80 mm...
A-a Gradient
  A-a

grad=(Calc PO2 )-(Measured PO2)
  A-a grad=150-(PCO2 /.8)- PO2
  Normal =10-20
  23%

will have no...
A-a Gradient in Patients with & without PE

Percent of Patients

(no prior history of Cardiac or Pulmonary disease)

A-a G...
D-Dimer
  A

degradation product of fibrin
  Monoclonal Ab test (RIA* & latex)
  NPV 90% (misses 1/10)
  PPV 30% (inco...
Lower Extremity Dopplers
 
 

 

PPV=78% NPV=88%
Advantages
–  noninvasive
–  inexpensive
Disadvantages
–  diff. with a...
Ventilation Perfusion Scans
Clinical Probability
80-100% 20-79% 0-19%
Hi

96%

88

56%

Int

66%

28%

16%

Low 40%

16%

...
Ventilation Perfusion Scan
 

PIOPED, ‘90
–  Interobserver agreement for V/Q readings 95%, 92%, 94% for
high, VLP, & NL s...
Pulmonary Angiogram
  Advantages
–  gold standard

  Disadvantages
–  invasive, $$$$
–  internists reluctance

  PIOPED...
CT Angiograms
 

Remy-Jardin, Radiology ‘96
– 
– 
– 
– 

75 conseq. Pts referred for PA prospectively
Sensitivity 91%, sp...
Goodman et al., 1995
PA of Central Vessels Only
CT
PE No PE
Total
Embolism present
6
1
7
Embolism absent
1
12
13
Total
7
1...
CT Angiograms
 

General Observations
–  Sensitivities 53-97%
–  Specificity 78-97%

 

Advantages
– 
– 
– 
– 

 

Cost...
Treatment
 

Unfractionated Heparin
–  5000 U bolus followed by 1250 U/hr
–  Maintain aPTT 2 - 2.5 normal
–  Recommend co...
Thrombolytic Therapy
 

Studies
–  Jerjes-Sanchez et al., J Thrombosis; 1995
–  Pts with hypotension & CHF were randomize...
Thrombolytic Therapy of PE
 

Standard Regimen*
–  100 mg tPA infusion over 2
hours

 

Unstable patients
–  .6mg/kg (ma...
The bad news
about thromboembolic disease
  Most

DVT’s are asymptomatic
  Most DVT’s produce PE
  Most PE’s are asympt...
Risk Factors for PE in patients without
Cardiac or Pulmonary disease
Immobile
Surgery
Malignancy
Thrombophlebitis

Trauma
...
Paradoxical embolism
Source most often in the calf

Reference: Stollberger: Ann Intern Med 1993;119

51
Electrocardiogram
  Normal

Sinus or Sinus Tachycardia 80%
  QRS axis change
–  Acute RAD
15%*
–  RBBB
8%
  T-wave abno...
CT Angiogram
 

Mayo et al., Radiology; 1997
–  139 nonconseq. pts. underwent CT, V/Q, & PA (if
indicated)
–  16% were ou...
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GEMC: The Emergency Department Management of Pulmonary Embolism

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Transcript of "GEMC: The Emergency Department Management of Pulmonary Embolism"

  1. 1. Project: Ghana Emergency Medicine Collaborative Document Title: The Emergency Department Management of Pulmonary Embolism Author(s): Rashmi Kothari (Kalamazoo College of Medical Science), MD, 2012 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. These lectures have been modified in the process of making a publicly shareable version. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/privacy-and-terms-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers. 1
  2. 2. Attribution Key for more information see: http://open.umich.edu/wiki/AttributionPolicy Use + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation License Make Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. 2 To use this content you should do your own independent analysis to determine whether or not your use will be Fair.
  3. 3. The Emergency Department Management of Pulmonary Embolism Rashmi U. Kothari, MD Kalamazoo College of Medical Science Borgess Research Institute 3
  4. 4. Goals PE is complication of venous thrombosis   PE is very, very common   Diagnosing only a very small % of PEs   The classic symptoms are uncommon   4
  5. 5. 20 y.o Male College Student with Hypotension & Questionable Syncope   Found knocking at neighbors door   BP=60/p P=125 R=24   EMS with MAST-trousers   PMH= none 5
  6. 6. Pulmonary Embolism 3rd most common cause of death   Most common fatal missed diagnosis   #2 cause of unanticipated death (after MI)   #1 cause of unexpected death on ventilator   #1 cause of death in orthopedics   #1 cause of death in pregnancy Papadakis: JAMA 1991; 265 Hecht: Zentralbl Allg Pathol 1984; 129 6
  7. 7. Fatal PE in-hospital 70% misdiagnosed antemortum 70% of PE cases unsuspected until autopsy Reference: Coon: Arch Surg 1976;111 30% have PE suspected before death 7
  8. 8. Mayo inpatient PE deaths Autopsies between 1985 - 1989   Listed cause of death correct in only 32%   Only 22% had a diagnostic workup for PE   ‘Classic’ symptoms absent in most cases   64% had no prophylaxis   46% had inadequate prophylaxis Reference: Morgenthaler: Mayo Clin Proc 1995; 70 8
  9. 9. Missed PE: autopsy incidence 33 published autopsy studies   33 studies between 1980 - 1995   150,000 autopsies   Fraction w/ missed diagnosis –  100% (highest) –  85% (average) –  55% (lowest) References too numerous to list 9
  10. 10. Fatal PE: missed Dx by age Dx missed in 90% of older patients Reference: Goldhaber: Am J Med 1982; 73 10
  11. 11. Inpatients vs out-of-hospital No difference in the incidence of PE found at autopsy Sperry: Hum Pathol 1990; 21 11
  12. 12. Mortality in PE By treatment type 35% 30% 25% 35% 20% 15% 10% 9% 5% 0% No treatment Heparin 5% Thrombolytics References: Bell: Am Heart J 1982;103 The Urokinase Pulmonary Embolism Trial: Circulation 1973;47 12
  13. 13. Mortality reduction w/ heparin 1358 medical admissions randomized 31% mortality reduction Reference: Halkin:Ann Intern Med1982; 96 13
  14. 14. Risk Factors for PE & DVT   Hypercoaguable state –  Protein S & C def -Anti-Thrombin III def* –  Pregnancy -BCP (>35 yo & smoker) –  Malignancy (colon & ovarian) Virchow’s Triad   Venostasis –  Obesity -Immobilization –  Heart disease (CHF, MI)   Vessel injury –  Surgery (especially pelvic surgery) –  Trauma 14
  15. 15. Risk Factors for PE Clinical Trial (n=117) Immobile Surgery Malignancy Thrombophlebitis Trauma Post-Partum <3 mos. No Risk Factors 66 (56% ) 63 (54%) 27 (23%) 16 (14%) 12 (10%) 5 (4%) 21 (18%) Autopsy* (n=92) 56 (61%) 33 (36%) 36 (39%) 22 (24%) 7 (8%) NA 11 (12%) References: Stein Chest 1991:100:598; Morgenthaler: Mayo Clin Proc 1995:70:417 15
  16. 16. Pathophysiology of PE   Majority caused by DVT –  15-30X more common –  50-90% with pelvic/lower ext. clot       Patent foramen ovale Air embolus (barotrauma, gyn surgery) Fat embolus (trauma) Source undetermined 16
  17. 17. Incidence of PE in patients with DVT Level No PE Asymp. PE Symp. PE Total PE 40 (56.5%) 4 (6.5%) 28 (39%) 32(45.5%) Proximal (n=292) 160 (55%) 72 (25%) 60 (20%) 132 (45%) Total 200 (55%) 76 (21%) 88 (24%) 164 (45%) Distal (n=72) (n=364) Reference: Monreal:Chest 1992102:677 17
  18. 18. PE from calf vein DVT Common and often fatal References: Moreno-Cabral Surgery 1976;80 Havig: Acta Chir Scand 1977;478 Kohn: Eur J Nucl Med 1987; 13 18
  19. 19. Autopsy source of PE Reference: Havig: Acta Chir Scand 1977;478 19
  20. 20. Chronic pulmonary HTN In 70% of those with recurrent PE Reference: Riedel: Chest 1982;81 20
  21. 21. 512 autopsy cases With isolated upper-extremity DVT Responsible for massive fatal PE 10% 90% Other Reference: Diebold: Pathol Res Pract 1991; 187 21
  22. 22. Catheter-associated DVT One-year autopsy study of PE   Autopsies with catheter DVT at one hospital   10 fatalities from massive PE   Source of embolus: –  Innominate vein –  Subclavian vein –  Superior vena cava Muller: Dtsch Med Wochenschr 1976; 101 22
  23. 23. PE from catheter-related DVT 20 cases of upper-extremity DVT associated with indwelling catheters   6/20 had PE   1 died from massive PE Monreal: Chest 1991; 99 23
  24. 24. Pathophysiology (cont)   Obstructs pulmonary vasculature   Increased physiologic deadspace in lung   Increases PA & RV pressures –  May cause Mitral regurg & cor pulmonale   Poor filling of L Ventricle causing hemodynamic compromise/collapse 24
  25. 25. Clinical Presentation Symptom Clinical Trials1 Autopsy2 Dyspnea 84% 59% Pleuritic Chest Pain 74% 8% Hemoptysis 27% 3% Apprehension 59% 17% Cough 53% 3% 1UPET & USPET 2Morgenthaler: Mayo Clin Proc 1995:70:417 25
  26. 26. Signs of PE Sign Tachypnea >16 Tachypnea >20 Tachycardia >100 Clinical Trials Autopsy* 92% 66% 70% NA 30% 54% Fever >37.5 C Low. Ext. edema Homan’s sign 43% 30% 24% 26% 4% NA *Morgenthaler: Mayo Clin Proc 1995:70:417 26
  27. 27. PE & asymptomatic DVT 2/3 with PE have no DVT symptoms asymptomatic DVT in patients with PE Reference: Walsh: J Obstet Gynaecol Br Commw 1974; 81 27
  28. 28. Clinical Dx of DVT unreliable 50% false positives and negatives In asymptomatic patients and in patients with pain, tenderness, and unilateral leg swelling Reference: Richards: Arch Int Med 1976; 136 28
  29. 29. ED Evaluation of PE Prospective, all pleuritic chest pain (n=173)   EKG, CXR, V/Q,   Angio (low, intermed., & high prob V/Q)   23% had PE   Immobilization, hx DVT, phlebitis, effusion*   20% had none of these risk factors*   Tierney: Med Dec Making 6:12. 1986 29 *Branch: Am J Med 75:671. 1983
  30. 30. Laboratory Tests   CXR   EKG   ABG   D-Dimer 30
  31. 31. Chest X-ray Non-specific & insensitive   Findings:   –  Normal –  Elevated hemi-diaphram –  Focal infiltrate (w/in 3 days) indistinguishable from pneumonia –  Effusion –  Atelectasis   30% 50% 30-50% 40-50% 50-60% Classic findings: –  Hampton’s hump –  Westermark Sign 7% 31
  32. 32. Electrocardiogram   Poor sensitivity & specificity   Findings: –  Tachycardia –  Non-specific ST-T wave changes –  Rt or Lt axis deviation –  P-pulmonale –  Atrial fibrillation –  S1Q3T3 –  S1S2S3 20% Reference: Bell: Am J Med: 62:355:1977 32
  33. 33. PO2 in Patients with & without PE Percent of Patients (no prior history of Cardiac or Pulmonary disease) Room Air PO2 (mmHg) Reference: Stein Chest 1991:100:598 33
  34. 34. Arterial Blood Oxygen   0% predictive value   17% PO2 > 80 mmHg   5% PO2 > 100 mmHg 34
  35. 35. ABG does not predict PE (120 possible PE, 54 with PE) PO2 Incidence of PE Incidence of PE below level above level 80 mm Hg 45/101 (44.6%) 9/19 (47.4%) 70 mm Hg 39/87 (44.8%) 15/33 (45.5%) 65 mm Hg 29/69 (42%) 25/51(49%) Reference: Menzolan: Am J Surg 137:543:1979 35
  36. 36. A-a Gradient   A-a grad=(Calc PO2 )-(Measured PO2)   A-a grad=150-(PCO2 /.8)- PO2   Normal =10-20   23% will have normal A-a gradient 36
  37. 37. A-a Gradient in Patients with & without PE Percent of Patients (no prior history of Cardiac or Pulmonary disease) A-a Gradient Reference: Stein Chest 1991:100:598 37
  38. 38. D-Dimer   A degradation product of fibrin   Monoclonal Ab test (RIA* & latex)   NPV 90% (misses 1/10)   PPV 30% (incorrect 7/10) 38
  39. 39. Lower Extremity Dopplers       PPV=78% NPV=88% Advantages –  noninvasive –  inexpensive Disadvantages –  diff. with acute on chronic –  worse PPV & NPV if asymp –  leg pain –  casts –  calf DVT’s (52% sens) Source undetermined 39
  40. 40. Ventilation Perfusion Scans Clinical Probability 80-100% 20-79% 0-19% Hi 96% 88 56% Int 66% 28% 16% Low 40% 16% 4% 6% 2% Nl 0% 73% had Int/Low prob scans High prob scans have PPV 88% Source undetermined PIOPED 90 40
  41. 41. Ventilation Perfusion Scan   PIOPED, ‘90 –  Interobserver agreement for V/Q readings 95%, 92%, 94% for high, VLP, & NL scans but dropped to 75% & 70% for IP & LP scans   Schugler et al ‘94 –  78% of intermediate scans & 92 % of low probability scans had no further testing –  But 35% of the former and 20% of the latter received anticoag. –  Leaving the decision to anticoagulate based on clinical grounds   Stein et al ‘91 –  Clinical evaluation of PE is non-specific 41
  42. 42. Pulmonary Angiogram   Advantages –  gold standard   Disadvantages –  invasive, $$$$ –  internists reluctance   PIOPED ‘90 –  2.5% mortality –  66% interobserver agreement for subsegmental PE’s   Stein ‘92 –  6% morb., 0.5% mortality   Sustman ‘82 12% requiring PA underwent procedure Source undetermined 42
  43. 43. CT Angiograms   Remy-Jardin, Radiology ‘96 –  –  –  –  75 conseq. Pts referred for PA prospectively Sensitivity 91%, specificity 78%, PPV 100%, NPV 89% 188 central PE’s on CT corresponded to PA Found isolated subsegmental clots in 5% on PA Angiography CT Findings Negative Positive Inconclusive Suboptimal Total Negative 25 0 4 3 32 Positive Inconclusive 1 0 39 0 3 0 0 0 43 0 Total 26 39 7 3 75 43
  44. 44. Goodman et al., 1995 PA of Central Vessels Only CT PE No PE Total Embolism present 6 1 7 Embolism absent 1 12 13 Total 7 13 20 PA of All Vessels CT PE No PE Embolism present 7 1 Embolism absent 4 8 Total 11 9 Total 8 12 20 44
  45. 45. CT Angiograms   General Observations –  Sensitivities 53-97% –  Specificity 78-97%   Advantages –  –  –  –    Cost Fast Close proximity to ED Alternative Dx Disadvantages –  ? Misses subseg. PE’s –  Not standard of care;yet –  IVP dye Source undetermined 45
  46. 46. Treatment   Unfractionated Heparin –  5000 U bolus followed by 1250 U/hr –  Maintain aPTT 2 - 2.5 normal –  Recommend concurrent heparin tx for 48 hr when starting Coumadin –  Most recommend 3 - 6 months of coumadin, or longer if they have a clotting disorder Agnelli et al., Int’l J. of Card.; 1998   LMWH –  Prospective randomized study have found nadroparine as safe and effective as unfrac. heparin for submassive PE –  Similar double blinded studies using tinzaprin Thery et al., Circ.; 1992 & Simonnneau et al, Haemostasis; 1996 46
  47. 47. Thrombolytic Therapy   Studies –  Jerjes-Sanchez et al., J Thrombosis; 1995 –  Pts with hypotension & CHF were randomized to anticoag or thrombolytics and anticoag –  Stopped after 8 pts b/c all 4 anticoag alone died, & all 4 thrombolytics and anticoag survived –  Wolfe et al., Am Heart J; 1994 –  101 pts (nl BP, RV dysfxn) randomized to rt-PA plus heparin or heparin alone –  No rt-PA pts had recurrent PE or died –  Of the 55 receiving heparin alone, 5 recurrent PE (2 fatal) 47
  48. 48. Thrombolytic Therapy of PE   Standard Regimen* –  100 mg tPA infusion over 2 hours   Unstable patients –  .6mg/kg (max=50mg) over 15 min *FDA approved 48
  49. 49. The bad news about thromboembolic disease   Most DVT’s are asymptomatic   Most DVT’s produce PE   Most PE’s are asymptomatic   DVT & PE causes death and disability even when there are no recognizable symptoms 49
  50. 50. Risk Factors for PE in patients without Cardiac or Pulmonary disease Immobile Surgery Malignancy Thrombophlebitis Trauma Post-Partum <3 mos. *p<.001 PE (n=117) 66 (56% ) 63 (54%) 27 (23%) 16 (14%) 12 (10%) 5 (4%) No PE (n=248) 81 (33%)* 78 (31%)* 38 (15%) 19 (8%) 25 (10%) 8 (3%) 50 Stein Chest 1991:100:598
  51. 51. Paradoxical embolism Source most often in the calf Reference: Stollberger: Ann Intern Med 1993;119 51
  52. 52. Electrocardiogram   Normal Sinus or Sinus Tachycardia 80%   QRS axis change –  Acute RAD 15%* –  RBBB 8%   T-wave abnormality 40%*   Depressed ST 25%   Elevated ST 16%* *Significantly more common in massive PE Stein:Progr. Cardiovasc Dis. 1974:17:247 52
  53. 53. CT Angiogram   Mayo et al., Radiology; 1997 –  139 nonconseq. pts. underwent CT, V/Q, & PA (if indicated) –  16% were outpts –  46/139 pts had a PE and 93/139 did not –  High prob V/Q in 30/46 (sens 65%) –  + CT in 40/46 (sens 87%), - CT in 88/93 (spec 95%) –  Overall, V/Q correct in 103/139 (74%) pts & CT was correct in 128/139 (92%) of cases –  Interobserver agreement (K) 0.61 for V/Q and 0.85 for CT 53
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