Zohair Al Aseri. MD, FCEM (UK). FRCPC (EM&CCM).

1. Pulmonary Emergencies Zohair Al Aseri. MD, FCEM (UK). FRCPC (EM&CCM). Consultant, Departments of Emergency Medicine & Critical Care. Chairman, Department of Emergency Medicine Director, Master Public Health.King Saud University Hospitals. Riyadh, KSA Email: zalaseri@ksu.edu.sahttp://fac.ksu.edu.sa/zalaseri Zohair Al Aseri FRCP EM & CCM

2. Pulmonary Embolism Risk Factors • 30% of pt has no provoking factors can be detected White RH.The epidemiology of venous thrombo embolism. Circulation 2003; 107(23Suppl1):I4–I8. Zohair Al Aseri. FRCP EM & CCM

3. Pulmonary Embolism Zohair Al Aseri. FRCP EM & CCM

4. Pulmonarym Embolism Clinical Characteristics PollackCV. Clinical characteristics, management, and outcomes of patients diagnosed with a cute PE in the ED: initial report of EMPEROR(Multi-Center Emergency Medicine Pulmonary Embolism in the Real World Registry). Jam CollCardiol 2011;57(6):700–706. Zohair Al Aseri. FRCP EM & CCM

5. Pulmonary Embolism Blood Work • 40% of the patients have normal arterial oxygen saturation • 20% a normal alveolar-arterial oxygen gradient Rodger MA, Diagnostic Value of Arterial Blood Gas Measurement in Suspected Pulmonary Embolism. AmJRespirCritCareMed 2000;162(6):2105–2108. Stein PD, Arterial blood gas analysis in the assessment of suspected acute pulmonary embolism. Chest 1996;109(1):78–81. Zohair Al Aseri. FRCP EM & CCM

6. Pulmonary Embolism Chest X-ray • Frequently abnormal • Usually nonspecific • Useful for excluding other causes of dyspnoea or chest pain. Zohair Al Aseri. FRCP EM & CCM

7. Pulmonary Embolism ECG RV strain: in more severe cases of PE • T waves inversion in leadsV1–V4 • a QR pattern in V1 • S1Q3T3 pattern • Incomplete or complete RBBB Sinus tachycardia • 40% of patients. Atrial fibrillation may be associated with acute PE GeibelA. Prognostic value of the ECG on admission in patients with acute major pulmonary embolism. EurRespirJ 2005;25(5):843–848 Zohair Al Aseri. FRCP EM & CCM

8. Pulmonary Embolism Clinical prediction rules for PE Zohair Al Aseri FRCP EM & CCM

9. Pulmonary Embolism Clinical prediction rules for PE Zohair Al Aseri FRCP EM & CCM

10. Zohair Al Aseri FRCP EM & CCM

11. Pulmonary Embolism MDCT {multi-detector computed tomographic angiography} • Adequate for excluding PE in a non high clinical probability. • Further investigation for negative CT and a high clinical probability is controversial. • CT segmental or more proximal level is adequate proof of PE in patients with a non-low clinical probability. Carrier M, Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. JThrombHaemost 2010;8(8):1716–1722. Zohair Al Aseri. FRCP EM & CCM

12. Pulmonary Embolism MDCT {multi-detector computed tomographic angiography} Isolated subsegmental PE on CT angiography • Clinical significance is questionable. • In 4.7%(2.5–7.6%) of patients with PE imaged by single detector CT angiography and 9.4% (5.5–14.2%) of those submitted to MDCT. Carrier M, Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. JThrombHaemost 2010;8(8):1716–1722. Zohair Al Aseri. FRCP EM & CCM

13. Pulmonary Embolism MDCT {multi-detector computed tomographic angiography} • ? role for CUS to exclude DVT • If no proximal DVT, decision to treat should be made on an individual basis, taking into account bleeding risk. Isolated subsegmental PE on CT angiography Stein PD, Diagnosis and management of isolated subsegmental pulmonary embolism: review and assessment of the options. ClinApplThrombHemost 2012;18(1):20–26. Zohair Al Aseri. FRCP EM & CCM

14. Pulmonary Embolism Ventilation–perfusion scintigraphy (V/Qscan) for low clinical probability and a normal chest X-ray in: • young (particularly female) patients • pregnancy • history of contrast medium-induced anaphylaxis and strong allergic history • severe renal failure • myeloma and paraproteinaemia Reid J H, Is the lung scan alive and well? Facts and controversies in defining the role of lung scintigraphy for the diagnosis of pulmonary embolism in the era of MDCT. EurJNuclMedMol Imaging 2009;36(3):505–521. Zohair Al Aseri. FRCP EM & CCM

15. Pulmonary Embolism Compression venous ultrasonography CUS • DVT was found in 70% of patients with proven PE. • CUS replaced venography for diagnosing DVT. • Sensitivity 90% and a Specificity of approximately 95% for symptomatic DVT Zohair Al Aseri. FRCP EM & CCM

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18. Pulmonary Embolism Management Haemodynamic and respiratory support • Modest 500mL • Vasopressors is often necessary • Norepinephrine Zohair Al Aseri. FRCP EM & CCM

19. PE MANAGEMENT PE RV afterload Hemodynamic Effects RV dilate LV prerload COP Septal shift RV O2 Consumption RV work RV ischemia Zohair Al Aseri. FRCP EM & CCM

20. Pulmonary Embolism Hypoxaemia • Usually reversed with oxygen. • If mechanical ventilation is required be carful not to increase intrathorcic pressure • PEEP should be applied with caution. • Low tidal volumes to keep the end-inspiratory plateau pressure 30cmH2O. Management Zohair Al Aseri. FRCP EM & CCM

21. Pulmonary Embolism Management Anticoagulation • Parenteral anticoagulation • Unfractionatedheparin (UFH) • LMWH • or fondaparinux • Over the first 5–10 days. Zohair Al Aseri. FRCP EM & CCM

22. PE MANAGEMENT Anticoagulation Why earlier is better? Recurrence rate 23% anticoagulated in the first day 4-6%, Hull RD, Raskob GE, Brant RF, et al. Relation between the time to achieve the lower limit of apt therapeutic range and recurrent venous thromboembolism during heparin treatment for deep venous thrombosis. Arch Intern Med. 2568-157: 2562;1997

23. Pulmonary Embolism Management Anticoagulation Low-molecular-weight heparins and Pentasaccharide (fondaparinux) approved for the treatment of PE Zohair Al Aseri FRCP EM & CCM

24. Pulmonary Embolism Management Anticoagulation • Heparin should overlap with vitamin K antagonist • can be followed by one of the new oral anticoagulants: dabigatran or edoxaban. Ifrivaroxaban or apixaban, • Oral treatment with one of these agents should be started directly or after a1–2 day of UFH, LMWH or fondaparinux. Zohair Al Aseri. FRCP EM & CCM

25. Pulmonary Embolism Vitamin K antagonists • Warfarin can be started at a dose of 10 mg in younger (e.g. ,60 years of age) healthy • 5mg in older patients and in those who are hospitalized. • Daily dose is adjusted according to the INR over the next 5–7 days, aiming for an INR level of 2.0–3.0 Zohair Al Aseri. FRCP EM & CCM

26. Pulmonary Embolism Management Anticoagulation • LMWH or fondaparinux are preferred over UFH for lower risk of major bleeding and HIT • UFH is recommended if: • Primary reperfusion is considered • Serious renal impairment (CR clearance ,30mL/min) • Severe obesity. Zohair Al Aseri. FRCP EM & CCM

27. Pulmonary Embolism Management Anticoagulation LMWH • No routine monitoring • periodic measurement of antifactor Xa activity (anti-Xa levels) may be considered during pregnancy. • Peak values of antifactor Xa activity should be measured 4 hours after the last injection and trough values just before the next dose of LMWH Would be due • Target range is • 0.6–1.0IU/ mL for twice daily • 1.0–2.0IU/Ml for once daily administration. Zohair Al Aseri. FRCP EM & CCM

28. Pulmonary Embolism Management Anticoagulation Fondaparinux • Selective factor Xa inhibitor • Daily SQ injection at weight adjusted doses, • No monitoring. • Not to be given with thrombolytic • No proven cases of HIT. • Contraindicated in patients with • severe renal insufficiency (Cr clearance ,30mL/min) • If (Cr clearance 30–50mL/min) dose should be reduced by 50 % in these patients. Zohair Al Aseri. FRCP EM & CCM

29. Pulmonary Embolism New oral anticoagulants Summary of results of the trials using NOACs in the treatment of VTE indicate that • these agents are noninferior (in terms of efficacy) • possibly safer (particularly in terms of major bleeding) than the standard heparin/VKA regimen Experience with NOACs is still limited but continues to accumulate. Zohair Al Aseri. FRCP EM & CCM

30. Phase III clinical trials with non-vitaminK-dependent new oral anticoagulants (NOACs) for the acute-phase treatment and standard duration of anticoagulation after VTE Pulmonary Embolism

31. Pulmonary Embolism Zohair Al Aseri. FRCP EM & CCM

32. Pulmonary Embolism Zohair Al Aseri. FRCP EM & CCM

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35. Pulmonary Embolism Fibrinolysis for Patients with Intermediate-Risk PE. nejm.org April 10, 2014 • Tenecteplase plus heparin with placebo plus heparin • in normotensive patients with intermediate-risk PE. • Eligible patients had RV dysfunction on echo or CT, as well as myocardial injury as indicated by a positive test troponin I or T.

36. Pulmonary Embolism Fibrinolysis for Patients with Intermediate-Risk PE. nejm.org April 10, 2014

37. Pulmonary Embolism Fibrinolysis for Patients with Intermediate-Risk PE. nejm.org April 10, 2014

38. Pulmonary Embolism Fibrinolysis for Patients with Intermediate-Risk PE. nejm.org April 10, 2014

39. Pulmonary Embolism Fibrinolysis for Patients with Intermediate-Risk PE. nejm.org April 10, 2014 Conclusions In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy increased the risk of major hemorrhage and stroke.

40. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism • Therefore, great caution is warranted when considering fibrinolytic therapy for hemodynamically stable patients with pulmonary embolism, right ventricular dysfunction, and a positive cardiac troponin test.

41. Pulmonary Embolism 1/2 thrombolysis in patients who are hemodynamically stable but had moderate PE evidenced on CTA Single-center, randomized, unblinded non-placebo-controlled study N=121 patients with moderate PE identified by CT criteria Randomization to either low-dose thrombolysis (n=61) or control (n=60) Mean follow-up: 28 months Primary Outcome: Pulmonary hypertension Secondary Composite Outcome: pulmonary hypertension or recurrent PE

42. Pulmonary Embolism The study was unblinded and only performed at a single center and the primary outcome of pulmonary hypertension reduction may not have a patient centered effect. • Randomization to: • Half Dose Thrombolysis: • tPA 0.5 mg/kg (max 50 mg), given as 10 mg bolus followed by remainder over 2 hours • Warfarin started on admission • Enoxaparin 1mg/kg subcutaneous twice daily or Heparin at 70U/kg bolus with dosing to keep PTT at 1.5-2x baseline • Control: same but no tPA

43. Pulmonary Embolism Venous filters • Usually Infrarenal portion of the inferior vena cava (IVC). • Suprarenal If thrombus is identified in the renal veins. • Indicated in • acute PE with absolute contraindications to anti coagulant drugs • In patients with recurrent PE despite adequate anticoagulation treatment Zohair Al Aseri. FRCP EM & CCM

44. Pulmonary Embolism Zohair Al Aseri. FRCP EM & CCM

45. Pulmonary Embolism PE in pregnancy Zohair Al Aseri. FRCP EM & CCM

46. Pulmonary Embolism PE in pregnancy • Estimated radiation (adapted from Bajc etal. (2009) and Chunilal etal. (2009) Zohair Al Aseri. FRCP EM & CCM

47. Pulmonary Embolism PE in pregnancy Epidural analgesia cannot be used unless LMWH has been discontinued at least 12 hs Treatment can be resumed 12–24 hs after removal of the epidural catheter. After delivery, heparin treatment may be replaced by anticoagulation with VKA. Zohair Al Aseri. FRCP EM & CCM

48. Pulmonary Embolism Zohair Al Aseri. FRCP EM & CCM