1. Acute Pulmonary Embolism 黃華桓 醫師 2008-Apr.-11

2. Outline ________________________________________ __ 1. Introduction 2. Epidemiology & Pathophysiology 3. Risk Factors 4. Diagnostic Approaches 5. Treatment 6. Pregnancy & APE 7. Conclusions

3. Introduction-1 most commonly originating from deep venous thrombosis ( DVT ) of the legs most commonly originating from deep venous thrombosis ( DVT ) of the legs Asymptomatic Asymptomatic incidentally discovered emboli incidentally discovered emboli massive embolism causing immediate death massive embolism causing immediate death

4. Introduction-2 Chronic sequelae of venous thromboembolism(VTE) (DVT & PE) Chronic sequelae of venous thromboembolism(VTE) (DVT & PE) post-thrombotic syndrome post-thrombotic syndrome chronic thromboembolic pulmonary H/T chronic thromboembolic pulmonary H/T

5. Introduction-3 Acute pulmonary embolism ( APE ) Acute pulmonary embolism ( APE ) may occur rapidly & unpredictably may occur rapidly & unpredictably may be difficult to diagnose may be difficult to diagnose

6. Introduction-4 Treatment can reduce the risk of death Treatment can reduce the risk of death appropriate primary prophylaxis : effective appropriate primary prophylaxis : effective rate of death in the next year: 1.5% vs. 0.4% rate of death in the next year: 1.5% vs. 0.4% Patients treated for APE appear to die of recurrent thromboembolism (1.5% ) Patients treated for APE appear to die of recurrent thromboembolism (1.5% ) patients treated for DVT (0.4% ) patients treated for DVT (0.4% )

7. Epidemiology & Pathophysiology

8. Epidemiology & Pathophysiology-1 Thrombi commonly form in deep veins in the calf Thrombi commonly form in deep veins in the calf propagate into the proximal veins, including & above the popliteal veins propagate into the proximal veins, including & above the popliteal veins from which they are more likely to embolize from which they are more likely to embolize

9. Epidemiology & Pathophysiology-2 About 79% of patients with PE have evidence of DVT in their legs About 79% of patients with PE have evidence of DVT in their legs PE occurs in up to 50% of patients with proximal DVT PE occurs in up to 50% of patients with proximal DVT Dual pulmonary circulation ( pulmonary & bronchial arteries ), pulmonary infarction : not usually present Dual pulmonary circulation ( pulmonary & bronchial arteries ), pulmonary infarction : not usually present

11. Epidemiology & Pathophysiology-3 APE, anatomical obstruction is the most important cause of compromised physiology APE, anatomical obstruction is the most important cause of compromised physiology release of vasoactive & bronchoactive agents (serotonin from platelets )---- deleterious ventilation – perfusion matching release of vasoactive & bronchoactive agents (serotonin from platelets )---- deleterious ventilation – perfusion matching

12. Epidemiology & Pathophysiology-4 As RV afterload increases, tension in RV wall rises As RV afterload increases, tension in RV wall rises dilatation, dysfunction, & ischemia of RV dilatation, dysfunction, & ischemia of RV Death results from RV failure. Death results from RV failure.

13. Epidemiology & Pathophysiology-5 VTE is a worldwide problem, esp. in people with known risk factors VTE is a worldwide problem, esp. in people with known risk factors Less common in certain regions, eg. Asia Less common in certain regions, eg. Asia Average annual incidence in US : 1 episode per 1000 registered patients Average annual incidence in US : 1 episode per 1000 registered patients US :300,000 people/year die from APE US :300,000 people/year die from APE Dx is often not made until autopsy Dx is often not made until autopsy Hospitalized pts are at particularly high risk Hospitalized pts are at particularly high risk

14. Risk Factors

15. Acquired Risk Factors Acquired Risk Factors Certain risk factors increase the likelihood Certain risk factors increase the likelihood Overall, acute medical illness may be the most common setting Overall, acute medical illness may be the most common setting Prolonged air or ground travel increases the risk Prolonged air or ground travel increases the risk eThrombosis:extended periods of sitting at a computer terminal eThrombosis:extended periods of sitting at a computer terminal Advancing age is another clear risk factor, with the risk increasing after age 40 Advancing age is another clear risk factor, with the risk increasing after age 40

17. Genetic Disorders & Thromboembolic Risk

18. Risk Factors for VTE

19. Virchow's classic triad of risk Hypercoagulability Hypercoagulability Stasis Stasis Venous injury Venous injury

20. Diagnostic Approaches

21. Clinical Manifestations -1 Recognition of the symptoms & signs of VTE may reduce diagnostic delays Recognition of the symptoms & signs of VTE may reduce diagnostic delays Symptoms of cough, palpitations, & dizziness & signs of fever, wheezing, & crackles : PE or concomitant illnesses Symptoms of cough, palpitations, & dizziness & signs of fever, wheezing, & crackles : PE or concomitant illnesses Tachypnea & tachycardia : common but nonspecific findings Tachypnea & tachycardia : common but nonspecific findings

22. Clinical Manifestations -2 Signs of pulm. HTN : elevated neck veins, loud P 2, right-sided gallop, & RV lift Signs of pulm. HTN : elevated neck veins, loud P 2, right-sided gallop, & RV lift Signs & symps. of VTE : highly suggestive but neither sensitive nor specific Signs & symps. of VTE : highly suggestive but neither sensitive nor specific extent of symptoms depends on the thromboembolic burden extent of symptoms depends on the thromboembolic burden massive PE:sudden onset of near syncope or syncope,hypotension,severe hypoxemia, EM dissociation, or cardiac arrest. massive PE:sudden onset of near syncope or syncope,hypotension,severe hypoxemia, EM dissociation, or cardiac arrest.

23. Clinical Manifestations -3 Leg pain, warmth, or swelling:DVT Leg pain, warmth, or swelling:DVT dyspnea or chest pain, either sudden onset or evolving over a period of days to weeks:APE dyspnea or chest pain, either sudden onset or evolving over a period of days to weeks:APE Pleuritic chest pain, a pleural rub (more peripheral emboli ) & hemoptysis: pulmonary infarction Pleuritic chest pain, a pleural rub (more peripheral emboli ) & hemoptysis: pulmonary infarction

24. Preliminary Lab. Testing & Pretest Probability -1 Hx., PE, & known risk factors Hx., PE, & known risk factors EKG, CXR, & ABG analysis EKG, CXR, & ABG analysis

25. Preliminary Lab. Testing & Pretest Probability -2 EKG:unexplained tachycardia:common in APE but nonspecific EKG:unexplained tachycardia:common in APE but nonspecific acute cor pulmonale: S1, Q3, T3 pattern, RBBB, P-wave pulmonale, or RAD : more common with massive embolism --- nonspecific acute cor pulmonale: S1, Q3, T3 pattern, RBBB, P-wave pulmonale, or RAD : more common with massive embolism --- nonspecific CXR: generally nondiagnostic CXR: generally nondiagnostic arterial oxygen tension may be normal arterial oxygen tension may be normal A – a oxygen difference may be normal A – a oxygen difference may be normal

26. Preliminary Lab. Testing & Pretest Probability -3 D-dimer test (+): VTE are possible diagnoses D-dimer test (+): VTE are possible diagnoses this test is nonspecific this test is nonspecific infection,other inflammatory states, cancer, & trauma infection,other inflammatory states, cancer, & trauma D-dimer testing is best considered together with clinical probability D-dimer testing is best considered together with clinical probability

27. Clinical Prediction Scores for Suspected APE- 1

28. Clinical Prediction Scores for Suspected APE- 2

29. Clinical Prediction Scores for Suspected APE- 3

30. Preliminary Lab. Testing & Pretest Probability -4 D-dimer test (-):with a low or moderate pretest probability, likelihood of VTE is low D-dimer test (-):with a low or moderate pretest probability, likelihood of VTE is low precludes the need for specific imaging studies precludes the need for specific imaging studies high pretest probability: imaging should be performed instead of D-dimer testing high pretest probability: imaging should be performed instead of D-dimer testing Other biomarkers: cardiac troponin levels, plasma levels of brain natriuretic peptide Other biomarkers: cardiac troponin levels, plasma levels of brain natriuretic peptide

31. Imaging Studies -1 Contrast-enhanced CT arteriography Contrast-enhanced CT arteriography the greatest sensitivity & specificity for detecting emboli in the main, lobar, or segmental pulmonary arteries the greatest sensitivity & specificity for detecting emboli in the main, lobar, or segmental pulmonary arteries false (+) CT arteriography : unusual false (+) CT arteriography : unusual sensitivity of spiral CT arteriography alone = 83%, combination of this & CT venography,up to 90% sensitivity of spiral CT arteriography alone = 83%, combination of this & CT venography,up to 90%

32. Imaging Studies -2 Ventilation – perfusion scan : diagnostic in the absence of cardiopulmonary disease Ventilation – perfusion scan : diagnostic in the absence of cardiopulmonary disease A normal perfusion lung scan effectively rules out APE A normal perfusion lung scan effectively rules out APE high probability scan:APE should be considered diagnostic, unless clinical suspicion is low or Hx. of PE with an identical previous scan high probability scan:APE should be considered diagnostic, unless clinical suspicion is low or Hx. of PE with an identical previous scan

33. Imaging Studies -3 if the clinical story strongly suggests PE,with a nondiagnostic V – P scan, Dx. should be rigorously pursued if the clinical story strongly suggests PE,with a nondiagnostic V – P scan, Dx. should be rigorously pursued nondiagnostic V – P scan : with low probability or with moderate probability but negative D-dimer test, no additional testing or therapy is indicated nondiagnostic V – P scan : with low probability or with moderate probability but negative D-dimer test, no additional testing or therapy is indicated

34. Imaging Studies -4 a recent study of 221 patients with susp. APE, MRI of the lung followed by MR venography ---successfully search for both DVT & PE a recent study of 221 patients with susp. APE, MRI of the lung followed by MR venography ---successfully search for both DVT & PE Echocardiography may reveal findings that strongly support hemodynamically significant PE, offering the potential to guide treatment Echocardiography may reveal findings that strongly support hemodynamically significant PE, offering the potential to guide treatment

36. Treatment

37. Anticoagulation-1 Bed rest is not recommended for DVT unless substantial pain & swelling Bed rest is not recommended for DVT unless substantial pain & swelling PE diagnosed, inpatient therapy with initial bed rest for 24 to 48 hrs : often recommended PE diagnosed, inpatient therapy with initial bed rest for 24 to 48 hrs : often recommended

38. Anticoagulation-2 APE (+):IV anticoagulation with LMW heparin, or standard, UF heparin should be initiated unless contraindicated APE (+):IV anticoagulation with LMW heparin, or standard, UF heparin should be initiated unless contraindicated Not thrombolytic, but decreasing the thromboembolic burden Not thrombolytic, but decreasing the thromboembolic burden If the suspicion of PE is high, parenteral anticoagulation should be considered even before imaging If the suspicion of PE is high, parenteral anticoagulation should be considered even before imaging

39. Anticoagulation-3 Warfarin can be initiated on day 1 of therapy Warfarin can be initiated on day 1 of therapy SC LMWH or weight-based UFH IV should be administered for at least 5 days until INR=2.0 to 3.0 for 2 consecutive days SC LMWH or weight-based UFH IV should be administered for at least 5 days until INR=2.0 to 3.0 for 2 consecutive days With standard heparin,aPTT checked Q6h until it is =1.5 to 2.5 X control With standard heparin,aPTT checked Q6h until it is =1.5 to 2.5 X control Achieving a therapeutic aPTT within 24 hours,reduce the risk of recurrence Achieving a therapeutic aPTT within 24 hours,reduce the risk of recurrence

40. Anticoagulation-4 LMWHs have advantages over UFH : greater bioavailability, more predictable dosing, SC delivery, & a lower risk of heparin-induced thrombocytopenia ( HIT ) LMWHs have advantages over UFH : greater bioavailability, more predictable dosing, SC delivery, & a lower risk of heparin-induced thrombocytopenia ( HIT ) Monitoring LMWH by anti – factor Xa : morbidly obese (weighing >150 kg) or very small ( 150 kg) or very small (<40 kg), pregnant, & very severe renal insufficiency or rapidly changing renal function

41. Anticoagulation-5 VTE require long-term anticoagulation to prevent extension & recurrence VTE require long-term anticoagulation to prevent extension & recurrence Documented VTE with transient risk factors should treat 3 to 6 months, but more extended treatment is appropriate when significant risk factors persist, idiopathic or previous episodes of VTE Documented VTE with transient risk factors should treat 3 to 6 months, but more extended treatment is appropriate when significant risk factors persist, idiopathic or previous episodes of VTE D-dimer levels may help guide decisions about the duration of therapy D-dimer levels may help guide decisions about the duration of therapy

42. Anticoagulation-6 Tx. with a direct thrombin inhibitor (e.g., argatroban or lepirudin) for HIT with thrombosis Tx. with a direct thrombin inhibitor (e.g., argatroban or lepirudin) for HIT with thrombosis Tx. with warfarin should not be initiated until disease process has been controlled & platelet count has returned to the normal range---potential for worsening thrombotic complications :venous limb gangrene & warfarin-induced skin necrosis Tx. with warfarin should not be initiated until disease process has been controlled & platelet count has returned to the normal range---potential for worsening thrombotic complications :venous limb gangrene & warfarin-induced skin necrosis

43. Placement of a Vena Caval Filter contraindications to anticoagulation contraindications to anticoagulation major bleeding during anticoagulation major bleeding during anticoagulation recurrent embolism under adequate therapy recurrent embolism under adequate therapy filters are effective in reducing the incidence of PE, they increase the subsequent incidence of DVT,but do not increase overall survival filters are effective in reducing the incidence of PE, they increase the subsequent incidence of DVT,but do not increase overall survival

44. Treatment of Massive PE PE causing hemodynamic instability PE causing hemodynamic instability resulting RV failure---compromised LV preload resulting RV failure---compromised LV preload If saline is infused for hypotension, it should be done with caution If saline is infused for hypotension, it should be done with caution Vasopressor therapy (e.g., dopamine) should be considered if BP is not rapidly restored Vasopressor therapy (e.g., dopamine) should be considered if BP is not rapidly restored

45. Complications of Thrombolytic Therapy-1 most widely accepted indication for thrombolytic therapy :proven PE with cardiogenic shock most widely accepted indication for thrombolytic therapy :proven PE with cardiogenic shock frequently considered : systemic hypotension without shock frequently considered : systemic hypotension without shock may be considered : severely compromised oxygenation or a massive embolic burden identified by image may be considered : severely compromised oxygenation or a massive embolic burden identified by image

46. Complications of Thrombolytic Therapy-2 The most devastating complication :ICH The most devastating complication :ICH retroperitoneal & GI bleeding & bleeding from surgical wounds or sites of recent invasive procedures retroperitoneal & GI bleeding & bleeding from surgical wounds or sites of recent invasive procedures Contraindications : intracranial, spinal, or ocular surgery or disease, recent major surgery or other invasive procedures, active or recent major bleeding, pregnancy, & clinically obvious risks of bleeding Contraindications : intracranial, spinal, or ocular surgery or disease, recent major surgery or other invasive procedures, active or recent major bleeding, pregnancy, & clinically obvious risks of bleeding

48. Prognosis The 3-month overall mortality :15 - 18% The 3-month overall mortality :15 - 18% Shock at presentation : increase in mortality by a factor of 3 to 7 Shock at presentation : increase in mortality by a factor of 3 to 7 post-thrombotic syndrome (chronic leg pain & swelling) & chronic thromboembolic pulmonary hypertension :possible long-term sequelae of APE post-thrombotic syndrome (chronic leg pain & swelling) & chronic thromboembolic pulmonary hypertension :possible long-term sequelae of APE

49. Prevention-1 Without prophylaxis, risk of VTE among acutely ill, hospitalized medical patients : as high as 15% Without prophylaxis, risk of VTE among acutely ill, hospitalized medical patients : as high as 15% Unfortunately, prophylaxis is grossly underused ( U.S. & international studies ) Unfortunately, prophylaxis is grossly underused ( U.S. & international studies ) Anticoagulant prophylaxis is more effective than lower-limb mechanical prophylaxis Anticoagulant prophylaxis is more effective than lower-limb mechanical prophylaxis

50. Prevention-2 After total hip or knee replacement, the risk of venous thrombosis : 50% or higher without prophylaxis After total hip or knee replacement, the risk of venous thrombosis : 50% or higher without prophylaxis Trauma & spinal cord injury :also very- high-risk scenarios Trauma & spinal cord injury :also very- high-risk scenarios Every hospitalized patient should be assessed for the need for prophylaxis Every hospitalized patient should be assessed for the need for prophylaxis

51. Pregnancy & Acute Pulmonary Embolism

52. Pregnancy & APE-1 increased risk for VTE : pregnancy, postpartum period,& hormone therapy increased risk for VTE : pregnancy, postpartum period,& hormone therapy Risk of a first episode of VTE= 5-fold as high in the postpartum period as during pregnancy Risk of a first episode of VTE= 5-fold as high in the postpartum period as during pregnancy Risk of PE = 15-fold as high during the postpartum period as during pregnancy Risk of PE = 15-fold as high during the postpartum period as during pregnancy

53. Pregnancy & APE-2 Low-dose oral contraceptives increase the risk of VTE : a factor of 2 to 5 Low-dose oral contraceptives increase the risk of VTE : a factor of 2 to 5 HRT increases the risk of VTE : a factor of 2 to 4 HRT increases the risk of VTE : a factor of 2 to 4 Pregnant patients with acute VTE require the same initial approach as other patients with regard to the need for parenteral anticoagulation, placement of an IVC filter, or embolectomy Pregnant patients with acute VTE require the same initial approach as other patients with regard to the need for parenteral anticoagulation, placement of an IVC filter, or embolectomy

54. Conclusions

55. Conclusions Untreated PE is associated with high mortality Untreated PE is associated with high mortality Suspected PE demands prompt diagnostic testing & assessment of risk factors & clinical probability, with empirical clinical assessment & a validated clinical prediction score when possible Suspected PE demands prompt diagnostic testing & assessment of risk factors & clinical probability, with empirical clinical assessment & a validated clinical prediction score when possible