1. CASE PRESENTATION Idan Khan

2. Case  71 y/o male brought in by EMS – Very healthy 71 y/o – Skiing all day no problems – c/o pain / tingling/ weakness to right arm, SOB

3. Case  Where and what to do??

4. Case  History – Skiing all morning – Afternoon at home acute onset SOB (5-10 min) – Resolved – Acute onset pain weakness and discoloration to right arm (unable to move arm) – Called EMS

5. Case  Past Hx – Healthy – Ex-smoker 15 pack yrs – High cholesterol on zocor

6. Case  EMS – Same hx as previous – O2 sat 80 % RA increased to 92% on NRB – BP 168/98, HR 115, RR 20 – Arm : white / purple

7. Case  ED Evaluation – Vitals: 159/99, HR 122, RR 20 – O2 sat 83% RA, increased to 96% NRB – Fit looking 71 y/o

8. Case  PE – A+O x3, speaking in full sentences, didn’t look labored but was tachypnic – H+N: normal – Chest: clear, no rub – CV: active precordium active precordium S1, S2 no S3 or S4, no murmurs S1, S2 no S3 or S4, no murmurs ? JVD ? JVD – Abdo: normal

9. Case  PE (con’t) –Right arm Purple in colour (from mid upper arm) Cool to touch Decreased cap refill No radial pulse Motor 4 -/ 5 (left 5/5)

10. Case  Investigations? –ECG –CXR –ABG???? –Blood work CBC, LYTES, PT, INR, CK

11. ECG

12. X-Ray

13. Case  CBC: –WBC 11 –Hb 160 –Plt 147  Lytes –Na 143, Cl 105, K 4.5, CO2 18 –INR 1.0, CK 93

14. Case  ABG 7.41 / 34 / 217 / 21 A-a gradient: (Alveolar – arterial) Alveolar: FIO2 x (BP – PP H2O) – (1.25 x PCO2) 1 x (665 – 47) – ( 1.25 x 21) = 618 – 26 = 592 Arterial : 217 A-a gradient : 592 – 217 = 375 (extremely elevated) Normal : (5-10) or ( age/4) + 4 - 71/4 + 4 = 22 mmHg

15. Case  DDX ?  What is your most likely diagnosis??

16. Case  What to do next? –Pt started on heparin (earlier) –ICU and vascular consulted  Any further investigations/treatment??

17. PE : Epidemiology  What about PE? –Epidemiology MC preventable hospital death MC undiagnosed hospital death True incidence unknown –650,000 cases / yr US –200,000 deaths

18. PE : Epidemiology  Epidemiology –1980 21% of all ED pts with pleuritic CP had a PE –Mortality Usually within the first hour But large # die with subsequent emboli Acute mortality correlates with RV function Long term mortality correlates with comorbid illness Age <40 mortality : 2.5% Age >40 mortality : 18% (some studies geriatrics 39% even when treated Overall untreated : 30% mortality Treated: 5% mortality

19. PE: Causes  Cause –90% from lower extremities Catheter related upper ext PE : up to 15% –PIOPED 50% immobilization within 3 months of PE 40% trauma or surgery –Neoplasm Responsible for 4% of thromboembolic disease Several studies: idiopathic PE (neoplasm eventually in ~ 9%)

20. PE: Clinical Features  Clinical Features –Younger pts: 30% no risk factors 60% normal vitals –97% have some combination of : Dyspnea, tachypnea, or pleuritic CP –Up to 10% will have syncope

21. PE: Physical Exam  Physical Exam –HR is normal in 70% pts –RR < 20 in 30% pts –Homans sign : flip a coin

22. PE: ECG  ECG –20 - 30% normal ECG –50% NSSTTW changes –RBBB, right axis deviation, ST depression, rarely S1, Q3, T3 –A-fib !

23. PE: CXR  CXR –84% pts will have an abn CXR –MS findings” Atelectasis, blunting of CP angle (effusion),elevated hemidiaphragm –Other signs: Hamptons Hump Westermark sign Fleischner sign

24. PE: A-a Gradient  A – a Gradient –>1/4 of all pts with PE will have P02 >80 –Some pts can have sat 100% RA –PIOPED 8-10% pts had normal A-a gradient A-a gradient nonspecific Not required in the work-up of PE !!!

25. Case  What next? –Echo Moderate TR Pulmonary artery pressures 90-100! Hypokinetic RV Normal LV function Positive bubble study !

26. PE: ECHO  ECHO –TTE: 85% sensitive for massive PE –TEE: 90% sen, up to 100% specific –Findings in PE Increased RV end diastolic pressures Increased PA pressures TR Abn septal movement

27. PE: CT Scan  CT Scan –Sensitivity: 88-95%, Specificity: 92- 97% –Adv: Can detect other pathology –Disadv: Limits visualization to fourth gen pulm arteries Hard to hold breath for scan!

28. Case  CT done –Bilateral filling defects (PE’s) –MASSIVE clot in the SVC/ and Right PA

29. Case  What would you do now? –Pt taken to ICU and underwent thrombolysis

30. Thrombolysis and PE  Mechanism –Converts plasminogen to plasmin –Breaks down fibrin –Clot dissolution  Agents –tPA, Urokinase, SK –tPA targets clot specific plasminogen/fibrin –Urokinase – human urine or cultured human renal cells

31. Thrombolysis and PE  Evidence for TT and PE –Case reports and case series in early 1960’s Improved hemodynamics and perfusion –UPET ( Urokinase Pulmonary Embolism Trial, 1970 ) 160 pts, heparin vs UK and heparin (12hr infusion) Hemodynamics/ lung perfusion improved at 24 hrs No mortality difference

32. Thrombolysis and PE  Evidence for TT and PE –Sharma et al (pts from UPET and USET) –Measured diffusion capacity and pulmonary blood volume at 2 wks and 1 yr –Improved in the thrombolytic therapy gp –Concluded: TT more complete resolution of clot beyond resolution of perfusion scan or angiography

33. Thrombolysis and PE  Evidence for TT and PE –Since UPET 8 smaller randomized trials –SK, UK, comparison etc. –All show variable benefit in either blood flow, perfusion but no mortality benefit –PIOPED (13 pts rtPA or heparin) Pulm vascular resistance : Diff at 1 hr gone at 2 hrs

34. Thrombolysis and PE  Evidence for TT and PE –Goldhaber et al (1993) N=101, heparin vs rtPA and heparin ECHO (3 and 24 hrs) and perfusion scans rtPA improved RV function and lung perfusion Trend to decreased recurrence of PE

35. Thrombolysis and PE  Evidence for TT and PE –Jerges et al 1995 –Small study n=8, massive PE with shock –SK vs heparin –Heparin 4/4 died –rtPA 0/4 died –First evidence of mortality benefit???

36. Thrombolysis and PE  Evidence for TT and PE –PE registry (1993-1994) n=1001 pts –RV dysfunction/ pulm hypertension (no shock) –rtPA (n=169) vs heparin (n=719) –Mortality: 4.7 vs 11.1% (ARR 3.4%, RRR 31%) –Recurrent PE: 7.7 vs 18.7% (ARR 11%, RRR 59%) –Needs to be validated in a large PRCT

37. Thrombolysis and PE  Evidence for TT and PE –Long term benefit (Sharma et al) –Right heart cath 7 yrs after PE and either TT or heparin –Heparin gp : higher PA pressures and higher pulmonary vascular resistance –TT gp : values normal

38. Thrombolysis and PE  Conclusion –TT results in more rapid clot resolution, perfusion and blood flow –No mortality difference in pts without shock (but may be due to small studies) –Possible mortality benefit in pts with shock!

39. Thrombolysis and PE  Which agent to use?? –SK for 24 hrs, UK for 12 hrs and rtPA for 2 hrs –Goldhaber et al rtPA 2 hr infusion, UK 24 hr infusion Earlier clot resolution and improved hemodynamics with rtPA at 2 hrs benefit gone at 24 hrs! Mortality no diff Increased hemorrhage in UK (double)

40. Thrombolysis and PE  Conclusion –All agents seem to be equal –rtPA has faster clot resolution but at 24 hrs no benefit

41. Thrombolysis and PE  Other conclusions –Intra-arterial TT is no better than systemic therapy (no increased risk of bleeding) –Time of administration: TT better if given early but can have benefit out to 14 days

42. Thrombolysis and PE  Complications –Major hemorrhage (fatal hem, ICH, hem requiring surgery or transfusion) : ~6% (heparin ~1.5%) –ICH : ~1% (death in ~50% ) Decreased in SK

43. Thrombolysis and PE  Indication For Thrombolysis 1) Hemodynamically unstable : shock or evidence of hypoperfusion 2) Hemodynamically stable: RV dysfunction? 3) ?? Large clot burden

44. Case  In ICU –Thrombolysis with improvement in RV function (demonstrated by repeat echo) –U/S residual clot in superficial femoral and brachial artery –IVC filter placed –Catheter placed tPA – no effect –Thrombectomy right arm –D/C to ward for monitoring –D/C home on lifelong anticoagulation

45. Case  Paradoxical embolus –Passage of venous embolus into the arterial circulation typically across an intracardiac shunt –Dx can only be inferred –Dx usually made if: Documented venous thromboembolism Acute arterial embolization ECHO evidence of right to left shunt Exclusion of a left sided source

46. Case  Paradoxical embolus –MC intra-cardiac defect – PFO Failed closure of the septum secundum –Frequency of PFO (autopsy) 29% (probe patent) 6% (pencil patent)

47. What if????  What if pt with antithrombin III deficiency presents with sx compatible with PE  How do you treat this pt.????