Acute Pulmonary Embolism

2008-Apr.-11

Outline__________________________________________IntroductionEpidemiology & PathophysiologyRisk Factors Diagnostic ApproachesTreatmentPregnancy & APEConclusions

Introduction-1most commonly originating from deep venous thrombosis ( DVT ) of the legsAsymptomaticincidentally discovered emboli massive embolism causing immediate death

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

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

Introduction-4Treatment can reduce the risk of deathappropriate primary prophylaxis : effectiverate 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 DVT (0.4% )

Epidemiology & Pathophysiology

Epidemiology & Pathophysiology-1Thrombi commonly form in deep veins in the calfpropagate into the proximal veins, including & above the popliteal veinsfrom which they are more likely to embolize

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

Epidemiology & Pathophysiology-3 APE, anatomical obstruction is the most important cause of compromised physiologyrelease of vasoactive & bronchoactive agents (serotonin from platelets )---- deleterious ventilationperfusion matching

Epidemiology & Pathophysiology-4As RV afterload increases, tension in RV wall risesdilatation, dysfunction, & ischemia of RVDeath results from RV failure.

Epidemiology & Pathophysiology-5VTE is a worldwide problem, esp. in people with known risk factorsLess common in certain regions, eg. AsiaAverage annual incidence in US : 1 episode per 1000 registered patientsUS :300,000 people/year die from APEDx is often not made until autopsyHospitalized pts are at particularly high risk

Risk Factors

Acquired Risk Factors

Certain risk factors increase the likelihoodOverall, acute medical illness may be the most common setting Prolonged air or ground travel increases the risk eThrombosis:extended periods of sitting at a computer terminalAdvancing age is another clear risk factor, with the risk increasing after age 40

Genetic Disorders & Thromboembolic Risk

Risk Factors for VTE

Virchow's classic triad of riskHypercoagulabilityStasisVenous injury

Diagnostic Approaches

Clinical Manifestations -1Recognition of the symptoms & signs of VTE may reduce diagnostic delaysSymptoms of cough, palpitations, & dizziness & signs of fever, wheezing, & crackles : PE or concomitant illnessesTachypnea & tachycardia : common but nonspecific findings

Clinical Manifestations -2Signs of pulm. HTN : elevated neck veins, loud P2, right-sided gallop, & RV liftSigns & symps. of VTE : highly suggestive but neither sensitive nor specificextent of symptoms depends on the thromboembolic burdenmassive PE:sudden onset of near syncope or syncope,hypotension,severe hypoxemia, EM dissociation, or cardiac arrest.

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

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

Preliminary Lab. Testing & Pretest Probability -2EKG:unexplained tachycardia:common in APE but nonspecificacute cor pulmonale: S1, Q3, T3 pattern, RBBB , P-wave pulmonale, or RAD : more common with massive embolism ---nonspecificCXR: generally nondiagnosticarterial oxygen tension may be normalAa oxygen difference may be normal

Preliminary Lab. Testing & Pretest Probability -3D-dimer test (+): VTE are possible diagnosesthis test is nonspecificinfection,other inflammatory states, cancer, & traumaD-dimer testing is best considered together with clinical probability

Clinical Prediction Scores for Suspected APE-1

Clinical Prediction Scores for Suspected APE-2

Clinical Prediction Scores for Suspected APE-3

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

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

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

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

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

Treatment

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

Anticoagulation-2APE (+):IV anticoagulation with LMW heparin , or standard, UF heparin should be initiated unless contraindicatedNot thrombolytic, but decreasing the thromboembolic burden If the suspicion of PE is high, parenteral anticoagulation should be considered even before imaging

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

Anticoagulation-4LMWHs have advantages over UFH : greater bioavailability, more predictable dosing, SC delivery, & a lower risk of heparin-induced thrombocytopenia ( HIT ) Monitoring LMWH by antifactor Xa : morbidly obese (weighing >150 kg) or very small (

Anticoagulation-5VTE require long-term anticoagulation to prevent extension & recurrenceDocumented 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 VTED-dimer levels may help guide decisions about the duration of therapy

Anticoagulation-6Tx. with a direct thrombin inhibitor (e.g., argatroban or lepirudin) for HIT with thrombosisTx. 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

Placement of a Vena Caval Filter

contraindications to anticoagulationmajor bleeding during anticoagulationrecurrent embolism under adequate therapyfilters are effective in reducing the incidence of PE, they increase the subsequent incidence of DVT,but do not increase overall survival

Treatment of Massive PEPE causing hemodynamic instabilityresulting RV failure---compromised LV preloadIf saline is infused for hypotension, it should be done with cautionVasopressor therapy (e.g., dopamine) should be considered if BP is not rapidly restored

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

Complications of Thrombolytic Therapy-2The most devastating complication :ICHretroperitoneal & 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

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

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

Prevention-2After 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

Pregnancy & Acute Pulmonary Embolism

Pregnancy & APE-1increased 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 PE = 15-fold as high during the postpartum period as during pregnancy

Pregnancy & APE-2Low-dose oral contraceptives increase the risk of VTE : a factor of 2 to 5HRT increases the risk of VTE : a factor of 2 to 4Pregnant 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

Conclusions

Conclusions 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