Acute Pulmonary Embolism

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

2. Outline__________________________________________ Introduction Epidemiology & Pathophysiology Risk Factors Diagnostic Approaches Treatment Pregnancy & APE Conclusions

3. Introduction-1 most commonly originating from deep venousthrombosis ( DVT ) of the legs Asymptomatic incidentallydiscovered emboli massive embolism causing immediate death

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

5. Introduction-3 Acute pulmonaryembolism ( APE ) may occur rapidly & unpredictably may be difficultto diagnose

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

7. Epidemiology & Pathophysiology

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

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

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

12. Epidemiology & Pathophysiology-4 As RV afterload increases, tensionin RV wall rises dilatation,dysfunction, & ischemia of RV Death resultsfrom RV failure.

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

14. Risk Factors

15. Acquired Risk Factors Certain risk factors increase the likelihood Overall, acute medical illness may be the most commonsetting Prolonged air or ground travel increases the risk eThrombosis:extendedperiods of sitting at a computer terminal Advancing age isanother 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 Stasis Venousinjury

20. Diagnostic Approaches

21. Clinical Manifestations -1 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 Tachypnea & tachycardia : commonbut nonspecific findings

22. Clinical Manifestations -2 Signs of pulm. HTN : elevated neck veins, loudP2, right-sided gallop, & RV lift Signs& symps. of VTE : highly suggestive but neither sensitive nor specific extent of symptoms depends on the thromboembolicburden massive PE:sudden onset ofnear syncope or syncope,hypotension,severe hypoxemia, EMdissociation, or cardiac arrest.

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

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

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

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

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 lowor moderate pretest probability, likelihood of VTE is low precludes the needfor specific imaging studies high pretestprobability: imaging should be performed instead ofD-dimer testing Other biomarkers: cardiactroponin levels, plasma levels of brain natriureticpeptide

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

32. Imaging Studies -2 Ventilation–perfusion scan : diagnosticin the absence of cardiopulmonary disease A normal perfusionlung scan effectively rules out APE high probability scan:APE should be considered diagnostic , unless clinical suspicion islow or Hx. of PE with an identicalprevious scan

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

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

36. Treatment

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

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

39. Anticoagulation-3 Warfarin canbe 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 With standard heparin,aPTT checked Q6h until it is =1.5 to 2.5 X control Achievinga therapeutic aPTT within 24hours ,reduce the risk of recurrence

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

41. Anticoagulation-5 VTE require long-termanticoagulation to prevent extension & recurrence Documented VTE with transientrisk factors should treat 3 to 6 months, but more extendedtreatment is appropriate when significant risk factors persist, idiopathic or previous episodesof VTE D-dimer levels may help guide decisions aboutthe duration of therapy

42. Anticoagulation-6 Tx. with a direct thrombin inhibitor (e.g., argatrobanor lepirudin) for HIT with thrombosis Tx. with warfarin should not be initiateduntil disease process has been controlled & plateletcount has returned to the normal range---potentialfor worsening thrombotic complications :venous limbgangrene & warfarin-induced skin necrosis

43. Placement of a Vena Caval Filter contraindications to anticoagulation major bleedingduring anticoagulation recurrent embolismunder adequate therapy 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 resulting RV failure---compromised LV preload 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

45. Complications of Thrombolytic Therapy-1 • most widely accepted indication for thrombolytic therapy :proven PE with cardiogenic shock • frequently considered :systemic hypotension without shock • 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 • 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

48. Prognosis • The 3-month overall mortality :15 - 18% • 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

49. Prevention-1 Without prophylaxis, risk of VTE among acutely ill, hospitalized medical patients : as high as 15% • Unfortunately, prophylaxis is grossly underused ( U.S. & international studies ) • 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 • Trauma & spinal cord injury :also very-high-risk scenarios • Every hospitalized patient should be assessed for the need for prophylaxis