1. Diagnosing Pulmonary Embolism in 2003 Dr. Peter Jones Emergency Medicine Specialist Auckland Hospital

2. Case 1 43f 5 days post LUSCS Sudden onset pleuritic R chest pain HR 104 WCC 13, D-Dimer 500-4000 3/7 later CxR blunting R CP angle CTPA negative Diagnosis: pleurisy Subsequently well

3. Case 2 19f smoker Dry cough and pleuritic central chest pain <1/7 RR 20 ABG –pO 2 10.3kPa (77mmHg) –A-a 3.7kPa (24mmHg – expected 9mmHg) D-Dimer <500, CxR normal, ECG normal CTPA negative, no positive (maybe) Anticoagulated 5 days V/Q ‘low probability’ day 4 Diagnosis: Chest pain ?cause

4. Case 3 29f 1/12 ago “blackout” 3/7 SOB and central chest pain (not pleuritic) 2/7 ago right leg cramp Occasional crepitation right base ECG RBBB, CxR normal ABG –pO 2 10kPa (75mmHg) –A-a 3.3kPa (21mmHg – expected 11mmHg) D-Dimer <500 Medical referral –Tender R costochondral junction,”flu” 1/12 ago Diagnosis: Costochondritis

5. Background PE Incidence: 23/100000/yr –Mortality 30% at 1 yr untreated, 2-8% treated 50% undiagnosed pre mortem Wide differential diagnosis Poor clinical signs Myriad of diagnostic strategies No consensus

6. Massive PE BTS 2003 Highly Likely If –Collapse / hypotension and –Unexplained hypoxia and –Engorged neck veins and –RV Gallop Bedside echocardiogram or CTPA <1hr

7. Non-massive PE The Literature Using a pre-investigation clinical score is useful –Defines a group of low risk patients that it is safe to use D- Dimer as a ‘rule out’ test Use Bayes’ theorem to calculate post test probability –The Se and Sp of each test needs to be known, these used to determine likelihood of PE given + or - test Post test probability of <2% accepted as sufficient to stop investigating for PE and look for other cause Post test probability >80% treat

8. Bayes’ Theorem Essay Towards Solving a Problem in the Doctrine of Chances Philosophical Transactions of the Royal Society of London (1764). Bayes theorem –Take pre test probability –Calculate odds –Multiply by test Likelihood Ratio to get post test odds –Calculate post test probability Thomas Bayes 1702-1761

9. PE Clinical Scores 1.Empiric (Best guess - Auckland) 2.Derived from logistic regression analysis of known risk factors, clinical and investigation findings - complex derivation –Wells et al. (Canada) –Wicki et al. (Switzerland) –Kline et al. (USA)

10. Wells et al. Clinical Model Simplified Thrombosis Haemostasis 2000; 83:416-20 976 patients, prevalence PE 17% 3Clinical Sn/Sx DVT Minimum leg swelling + pain on palpation deep veins 3Alternative diagnosis less likely than PE 1.5HR >100 1.5Immobilisation or surgery previous 4 weeks 1.5Previous VTE 1Haemoptysis 1Malignancy Treated in last 6/12 or palliative

11. Wells et al. Score%Pts%PE <2Low403.6 2-6Mod5320.5 >6High766.7 <=4Unlikely717.8 >4Likely2940.7 >2500 patients several studies

12. Wicki et al. Arch. Int. Med. 2001:161, 92-98 986 ED patients prevalence 27% ScoreRisk%Pts%PE <4Low4910 4-8Int.4438 >8High681

13. Kline et al Ann Emerg. Med. 2002:39:2, 144-152 934 ED patients, prevalence of PE 19% Category%Pts%PE Safe7913.3 Unsafe2142 HR/SBP >1 or Age > 50 sO 2 < 95% (normal lungs) Unilateral leg swelling Recent surgery Haemoptysis If yes to any of the above, asked in this order, then ‘unsafe’ to test with D-Dimer

14. PE Clinical Scores

15. PE Investigations D-Dimer Assays use an antibody directed against the D-dimer peptide, which is a product of fibrin breakdown Currently using latex agglutination test –Sufficiently inaccurate so that post test probability 9% in low risk patients, 60% in high risk (empiric score) –Negative LR 0.38, Positive LR 3.5 Rapid ELISA test now available (Vidas) –Negative LR 0.07, Positive LR 1.6 –Post test probability <2% in low risk group, 23% in high risk group

16. PE Investigations CTPA Multitude of papers Modern multi-slice scanners accurate –Probably as good as pulmonary angiography –Sn 95%, Sp95% –-ve LR 0.06, +ve LR 19 Can reveal other diagnosis Some scans will be equivocal Relative contraindications –Renal impairment –Young women Absolute contraindication –Contrast Allergy

17. PE Investigations Compression Ultrasound NO LEG SIGNS 3 studies Approx 2000 patients NLR 0.39-0.73 LEG SIGNS 5 Studies >2000 patients NLR 0.02-0.16

18. Investigations Pulmonary Angiography –?Consigned to history VQ scan –May have a place if CTPA contraindicated –NRL 0.1 only 14% have normal/near normal scans 9% of these had PE in PIOPED

19. Algorithms Plethora of published algorithms with various strategies Aim to rule out PE with post test probability <2% Recently published (2003) –British Thoracic Society –Emergency Medicine

20. Currently at Auckland Applying Bayes’ Theorem to the presented cases, using our current tests

21. A Very Safe Algorithm SCGH Perth WA

22. BTS guidelines Thorax 2003, 58:470-484 2.5-10%

23. RMO Handbook 4% 6%

24. Ignoring the Pretest Probability Parallel stream in the literature Assumptions –“A negative Vidas D-Dimer rules out PE” –“A negative CTPA rules out PE” Problems –Vidas D-Dimer will miss PE Sensitivity 90-100%, NLR 0.05-0.22 –50-85% of patients require CTPA, 5-23% have PE –CTPA will miss PE / be equivocal Sensitivity 95%, specificity 95%, NLR 0.06

25. Well’s Score 4 or less Unlikely PE Well’s Score >4 Likely PE Vidas D-Dimer CTPA / VQ - Other cause Post test prob > 75% Treat + + Proposed Algorithm Compression US Well’s Unlikely - + - 2.2% CTPA 3.6% VQ Well’s likely

26. Algorithm Implications Regardless of chosen algorithm, imaging for PE will increase markedly (diagnosis of PE will also increase)

27. Thomas Bayes 1736 “..why, therefore, if I am half blind, must I take for my guide one that cannot see at all?”

28. Selected References Clinical Score PE –Wells PS et Al. Thromb. Haemost. 2000: 83;416-20 –Wicki et Al Arch. Int. Med. 2001:161, 92-98 –Kline et al Ann Emerg. Med. 2002:39:2, 144-152 DVT –Wells PS et al. Thromb. Haemost. 1999 81 493-7 D-Dimer –Kline paper above (good summary of the issues) –Sijens PE et al. Thromb. Haemost. 2000: 84; 156-9 CTPA vs Pulmonary Angio –Wells PS et al. Clin Chest Med 24 2003 13-28 Chapter ‘Diagnosis of PE: When is imaging needed?’ –Kline et al. Ann Emerg Med 35 (2) 2000; 168-80 Compression Ultrasound –Turkstra et al. Ann Int med 1997 126(10) 775-781 –Heijboer H et al. NEJM 1993 329 (19) 1365-1369 –Perrier A et Al Lancet 1999 353 190-195 Strategies PE –Perrier A et al Lancet 1999 353 190-195 –Musset et al. Lancet 2002 360 1914-1920 –Chagnon et al. Am J Med 2002 113: 269-275 –BTS Standards of care committee Thorax 2003 58 470-83 British Thoracic Society Guidelines –Mountain D. emergency medicine 2003 15 (3); 250-62 –Fedullo PF et al. NEJM 2003 349 (13); 1247-56 –Kline JA and Wells PS: Ann Emerg Med August 2003 42:2 266-276 DVT –Wells et al NEJM 2003 349 (13); 1227-35 (and many others)