1. 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism 2014.09.29 호흡기내과 R4 황인경

2. Contents 1.preamble 2.Introduction 3.Diagnosis 4.Prognosis assessment 5.Treatment in the acute phase 6.Duration of anticoagulation 7.Chronic thromboembolic pulmonary hypertension 8.Specific problems  Pathophysiology

3. Pathophysiology Acute pulmonary embolism (PE) interferes with both the circulation and gas exchange Pulmonary artery pressure increases – Anatomical obstruction and PE-induce vasoconstriction lead to an increase in pulmonary vascular resistance and a proportional decrease in arterial compliance The abrupt increase in pulmonary vascular resistance results in RV dilation, decreased RV contractility The prolongation of RV contraction time results that left ventricular (LV) filling is impeded in early diastole, and this leads to a reduction of CO and contribute to systemic hypotension and hemodynamic instability

4. Pathophysiology

5. Respiratory failure in PE is predominantly a consequence of hemodynamic disturbances zones of reduced flow in obstructed vessels, zones of overflow in non-obstructed vessels, result in ventilation-perfusion(V/Q) mismatch, which contributes to hypoxemia In about 1/3 patients, right-to-left shunting through a patent foramen ovale may lead to severe hypoxemia and an increased risk of paradoxical embolization and stroke ‘pulmonary infarction’: small distal emboli may create areas of alveolar haemorrhage resulting in hemoptysis, pleuritis, and pleural effusion

6. Clinical classification of pulmonary embolism severity

7. Diagnosis

8. Assessment of clinical probabilty 10% 30% 65%

12. Treatment in the acute phase

13. 1. Hemodynamic and respiratory support Acute RV failure is the leading cause of death in patients with high-risk PE Modest (500 mL) fluid, not aggressive volume expansion, challenge may help to increase cardiac index (CI) in patients with PE, low CI, and normal BP Norepinephrine appears to improve RV function via a direct positive inotropic effect in hypotensive patients Dobutamine and/or dopamine may be considered for patients with PE, low CI, and normal BP; however, raising the CI may aggravate the V-Q mismatch Epinephrine may exert beneficial effects in patients with PE and shock

14. 1. Hemodynamic and respiratory support Vasodilators decrease pulmonary arterial pressure and pulmonary vascular resistance, but the main concern is the lack of specificity for the pulmonary vasculature Inhalation of nitric oxide may improve the hemodynamic status and gas exchange of patients with PE. levosimendan may restore RV function in acute PE by combining pulmonary vasodilation with an increase in RV contractility Hypoxemia is usually reversed with administration of oxygen When MV is required, PEEP should be applied with caution and Low tidal volumes (~6 mL/kg) should be used to keep the end-inspiratory plateau pressure, 30 cmH2O

15. 2. Anticogaulation 1. Parenteral anticoagulation – In patients with high or intermediate clinical probability for PE, parenteral anticoagulation should be initiated while awaiting the results of diagnostic tests – LMWH or fondaparinux (SC) are preferred over UFH for initial anticoagulation in PE (lower risk of major bleeding and heparin-induced thrombocytopenia (HIT)) – UFH (IV) is recommended for pts in whom primary reperfusion is considered, for those with serious renal impairment (CrCL< 30 mL/min), or severe obesity – Fondaparinux is a selective factor Xa inhibitor administered once daily without the need for monitoring

16. 2. Anticogaulation 2. Vitamin K antagonist (VKA) – Oral anticoagulants should be initiated on the same day as the parenteral anticoagulant – VKAs have been the ‘gold standard’ in oral anticoagulation for more than 50 years for PE – VKA with UFH, LMWH, or fondaparinux should be continued for at least 5 days and until INR 2.0-3.0 – Warfarin can be started at a dose of 10 mg in younger, and 5 mg in older pts and hospitalized pts  The daily dose is adjusted according to the INR

17. 2. Anticogaulation 2. New oral anticoagulants (NOACs) 1)Dabigatran: direct thrombin inhibitor 2)Rivaroxaban: direct factor Xa inhibitor (15 mg bid for 3 weeks, then 20 mg qd) 3)Epixaban: direct factor Xa inhibitor (10 mg bid for 7 days, then 5 mg bid) 4)Edoxaban: direct factor Xa inhibitor  alternatives to standard treatment  not recommend in pts with severe renal failure – rivaroxaban, dabigatran and apixaban are approved for treatment of VTE in the European Union; edoxaban is currently under regulatory review

19. 3. Thrombolytic treatment 4. Surgical embolectomy 5. Percutaneous catheter-directed treatment 6. Venous filters 7. Early discharge and home treatment

20. 8. Therapeutic strategies

21. Pulmonary severity index

23. 8. Therapeutic strategies 1. High risk pulmonary embolism 1)Hemodynamic and respiratory support 2)IV UFH 3)Primary reperfusion treatment Systemic thrombolysis : TOC Surgical embolectomy: pts with contraindications to thrombolysis Alternative to surgery, percutaneous catheter directed treatment

25. 8. Therapeutic strategies 2. Intermediate or low risk pulmonary embolism – LMWH or fondaparinux without monitoring: TOC for most cases, unless severe renal dysfunction – Low risk: A/C & early discharge and outpatient Tx – Intermediate-high risk: systemic thrombolysis, not routinely recommend, should be considered if sign of hemodynamic decompensation – Intermeiate-low risk: A/C & hospitalization

26. Duration of anticoagulation

27. Main findings of clinical trials were various duration of Tx – patients with PE should receive at least 3 months of anticoagulant treatment – the risk of recurrence if anticoagulants are stopped after 6 or 12 mo can be similar to that after 3 mo – indefinite treatment reduces the risk for recurrent VTE by about 90%, but this benefit is partially offset by a 1% or higher annual risk of major bleeding  anticoagulants are discontinued when the perceived risk of bleeding and the inconvenience of treatment outweigh the risk of recurrent VTE

28. Duration of anticoagulation At least 3–6 months of treatment with LMWH (dalteparin) are recommended for patients with VTE and cancer ; unclear to treat after the first 6month, but treatment with LMWH or VKA is recommended as long as disease is active For patients with provoked PE (such as surgery, trauma, immobilization, pregnancy, oral contraceptive use temporally) treatment with a VKA for 3 months is preferable For patients with Unprovoked PE, on the balance between the recurrence risk and bleeding risk, should be treated with VKA for at least 3 months Lifelong treatment is recommended for most pts with a 2 nd unprovoked DVT or PE

29. New oral anticoagulant for extended treatment the results of the trials using NOACs in the extended treatment of VTE are both effective (prevention of symptomatic or fatal recurrence of VTE) and safe (particularly major bleeding)-probably safer than standard VKA regimens