acute pulmonary embolism 黃華桓 醫師 2008-apr.-11. outline...

Acute Pulmonary EmbolismAcute Pulmonary Embolism

黃華桓 醫師黃華桓 醫師2008-Apr.-112008-Apr.-11

OutlineOutline____________________________________________________________________________________

1.1. IntroductionIntroduction

2.2. Epidemiology & PathophysiologyEpidemiology & Pathophysiology

3.3. Risk Factors Risk Factors

4.4. Diagnostic ApproachesDiagnostic Approaches

5.5. TreatmentTreatment

6.6. Pregnancy & APEPregnancy & APE

7.7. ConclusionsConclusions

Introduction-1Introduction-1

• most commonly originating from most commonly originating from deep venousdeep venous thrombosis ( DVT ) of thrombosis ( DVT ) of the legsthe legs

• AsymptomaticAsymptomatic

• incidentallyincidentally discovered emboli discovered emboli

• massive embolism causing massive embolism causing immediate deathimmediate death

Introduction-2Introduction-2

• Chronic sequelae of venous Chronic sequelae of venous thromboembolism(VTE) (DVT & PE)thromboembolism(VTE) (DVT & PE)

• post-thrombotic syndromepost-thrombotic syndrome

• chronic thromboembolic pulmonary chronic thromboembolic pulmonary H/TH/T

Introduction-3Introduction-3

• Acute pulmonaryAcute pulmonary embolism ( APE )embolism ( APE )

• may occur rapidly & unpredictablymay occur rapidly & unpredictably

• may be difficultmay be difficult to diagnoseto diagnose

Introduction-4Introduction-4

• Treatment can reduce the risk of deathTreatment can reduce the risk of death

• appropriateappropriate primary prophylaxis : primary prophylaxis : effectiveeffective

• rate of death in the next year: 1.5% vs.rate of death in the next year: 1.5% vs.

0.4%0.4%

• Patients treated forPatients treated for APE appear to die APE appear to die of recurrent thromboembolism (1.5% )of recurrent thromboembolism (1.5% )

• patientspatients treated for DVT (0.4% )treated for DVT (0.4% )

Epidemiology & Epidemiology & PathophysiologyPathophysiology

Epidemiology & Epidemiology & Pathophysiology-1Pathophysiology-1

• Thrombi commonly form in deep Thrombi commonly form in deep veinsveins in the calfin the calf

• propagate into the proximal veins, propagate into the proximal veins, includingincluding & above the popliteal veins& above the popliteal veins

• from which they are more likelyfrom which they are more likely to to embolizeembolize

Epidemiology & Epidemiology & Pathophysiology-2Pathophysiology-2

• About 79% of patients with PE have About 79% of patients with PE have evidence of DVT in their legsevidence of DVT in their legs

• PE occurs in up to 50% of patients PE occurs in up to 50% of patients with proximal DVTwith proximal DVT

• Dual pulmonary circulation Dual pulmonary circulation ( pulmonary( pulmonary & bronchial arteries ), & bronchial arteries ), pulmonary infarction : not usuallypulmonary infarction : not usually

presentpresent

Epidemiology & Epidemiology & Pathophysiology-3Pathophysiology-3

• APE, anatomical obstructionAPE, anatomical obstruction is the is the most important cause of most important cause of compromised physiologycompromised physiology

• release of vasoactive & release of vasoactive & bronchoactive agents (serotonin from bronchoactive agents (serotonin from platelets )---- deleterious ventilationplatelets )---- deleterious ventilation––perfusionperfusion matchingmatching

Epidemiology & Epidemiology & Pathophysiology-4Pathophysiology-4

• As RV afterload increases, tensionAs RV afterload increases, tension in in RV wall risesRV wall rises

• dilatation,dilatation, dysfunction, & ischemia of dysfunction, & ischemia of RVRV

• Death resultsDeath results from RV failure.from RV failure.

Epidemiology & Epidemiology & Pathophysiology-5Pathophysiology-5

• VTE is a worldwide problem, esp. in VTE is a worldwide problem, esp. in peoplepeople with known risk factorswith known risk factors

• Less common in certain regions, eg. AsiaLess common in certain regions, eg. Asia

• Average annual incidence in US : 1 Average annual incidence in US : 1 episodeepisode per 1000 registered patientsper 1000 registered patients

• US :300,000US :300,000 people/year die from APEpeople/year die from APE

• Dx is often not made until autopsyDx is often not made until autopsy

• HospitalizedHospitalized pts are at particularly high pts are at particularly high riskrisk

Risk FactorsRisk Factors

Acquired Risk FactorsAcquired Risk Factors

• Certain risk factors increase the likelihoodCertain risk factors increase the likelihood

• Overall, acute medical illness may be the Overall, acute medical illness may be the most commonmost common setting setting

• Prolonged air or ground travel increases Prolonged air or ground travel increases the riskthe risk

• eThrombosis:extendedeThrombosis:extended periods of sitting periods of sitting at a computer terminalat a computer terminal

• Advancing age isAdvancing age is another clear risk factor, another clear risk factor, with the risk increasing after with the risk increasing after age 40 age 40

Genetic Disorders & Thromboembolic Genetic Disorders & Thromboembolic RiskRisk

Risk Factors for VTERisk Factors for VTE

Virchow's classic triad of Virchow's classic triad of riskrisk

• HypercoagulabilityHypercoagulability

• StasisStasis

• VenousVenous injuryinjury

Diagnostic ApproachesDiagnostic Approaches

Clinical ManifestationsClinical Manifestations -1 -1

• Recognition of the symptoms & signs Recognition of the symptoms & signs of VTE may reduce diagnostic delaysof VTE may reduce diagnostic delays

• Symptoms of cough,Symptoms of cough, palpitations, & palpitations, & dizziness & signs of fever,dizziness & signs of fever, wheezing, wheezing, & crackles : PE or & crackles : PE or concomitant concomitant illnessesillnesses

• Tachypnea & tachycardia : commonTachypnea & tachycardia : common

but nonspecific findingsbut nonspecific findings

Clinical ManifestationsClinical Manifestations -2 -2

• Signs of pulm. HTN : elevated neck veins, Signs of pulm. HTN : elevated neck veins, loudloud PP22, right-sided gallop, & RV lift, right-sided gallop, & RV lift

• SignsSigns & symps. of VTE : highly suggestive & symps. of VTE : highly suggestive but neither sensitive nor specificbut neither sensitive nor specific

• extent of symptoms depends on the extent of symptoms depends on the thromboembolicthromboembolic burdenburden

• massive PE:sudden onset ofmassive PE:sudden onset of near syncope or near syncope or syncope,hypotension,severe hypoxemia, EMsyncope,hypotension,severe hypoxemia, EM

dissociation, or cardiac arrest.dissociation, or cardiac arrest.

Clinical ManifestationsClinical Manifestations -3 -3

• Leg pain, warmth, or swelling:DVTLeg pain, warmth, or swelling:DVT

• dyspnea ordyspnea or chest pain, either sudden chest pain, either sudden onset or evolving over a periodonset or evolving over a period of of days to weeks:APEdays to weeks:APE

• Pleuritic chest pain , a pleural rub Pleuritic chest pain , a pleural rub (more peripheral emboli ) & (more peripheral emboli ) & hemoptysis: pulmonary infarctionhemoptysis: pulmonary infarction

Preliminary Lab. Testing & Pretest ProbabilityPreliminary Lab. Testing & Pretest Probability -1-1

• Hx., PE, & known risk factorsHx., PE, & known risk factors

• EKG,EKG, CXR, & ABG analysisCXR, & ABG analysis

Preliminary Lab. Testing & Pretest ProbabilityPreliminary Lab. Testing & Pretest Probability -2-2

• EKG:unexplained tachycardia:common in EKG:unexplained tachycardia:common in APE but nonspecificAPE but nonspecific

• acuteacute cor pulmonale: S1, Q3, T3 pattern, cor pulmonale: S1, Q3, T3 pattern, RBBB , P-wave pulmonale, or RAD : more RBBB , P-wave pulmonale, or RAD : more commoncommon with massive embolism ---with massive embolism ---nonspecificnonspecific

• CXR: generally nondiagnosticCXR: generally nondiagnostic

• arterialarterial oxygen tension may be normaloxygen tension may be normal

• AA––aa oxygen difference may be normaloxygen difference may be normal

Preliminary Lab. Testing & Pretest ProbabilityPreliminary Lab. Testing & Pretest Probability -3-3

• D-dimerD-dimer test (+): VTE are possible test (+): VTE are possible diagnosesdiagnoses

• this test is nonspecificthis test is nonspecific

• infection,other inflammatory states, infection,other inflammatory states, cancer,cancer, & trauma& trauma

• D-dimer testing is best considered D-dimer testing is best considered together with clinicaltogether with clinical probabilityprobability

Clinical Prediction Scores for Clinical Prediction Scores for Suspected APE-1Suspected APE-1

Clinical Prediction Scores for Clinical Prediction Scores for Suspected APE-2Suspected APE-2

Clinical Prediction Scores for Clinical Prediction Scores for Suspected APE-3Suspected APE-3

Preliminary Lab. Testing & Pretest ProbabilityPreliminary Lab. Testing & Pretest Probability -4-4

• D-dimer test (-):with a lowD-dimer test (-):with a low or moderate or moderate pretest probability, likelihood of VTE is low pretest probability, likelihood of VTE is low

• precludes the needprecludes the need for specific imaging for specific imaging studiesstudies

• high pretesthigh pretest probability: imaging should be probability: imaging should be performed instead ofperformed instead of D-dimer testingD-dimer testing

• Other biomarkers: cardiacOther biomarkers: cardiac troponin levels, troponin levels, plasma levels of brain natriureticplasma levels of brain natriuretic peptidepeptide

Imaging StudiesImaging Studies -1 -1

• Contrast-enhanced CT arteriographyContrast-enhanced CT arteriography

• thethe greatest sensitivity & specificity for greatest sensitivity & specificity for detecting emboli indetecting emboli in the main, lobar, or the main, lobar, or segmental pulmonary arteriessegmental pulmonary arteries

• false (+) CT arteriographyfalse (+) CT arteriography : unusual: unusual

• sensitivity of spiral CT arteriographysensitivity of spiral CT arteriography

alone = 83%, combination of this &alone = 83%, combination of this & CT CT venography ,up to 90%venography ,up to 90%

Imaging StudiesImaging Studies -2 -2

• VentilationVentilation––perfusion scan : diagnosticperfusion scan : diagnostic in in the absence of cardiopulmonary diseasethe absence of cardiopulmonary disease

• A normal perfusionA normal perfusion lung scan effectively lung scan effectively rules out APErules out APE

• high probability scan:APE should be high probability scan:APE should be considered diagnostic , unless clinical considered diagnostic , unless clinical suspicion issuspicion is low or Hx. of PE with an low or Hx. of PE with an identicalidentical previous scanprevious scan

Imaging StudiesImaging Studies -3 -3

• if the clinical story stronglyif the clinical story strongly suggests suggests PE,with a nondiagnostic VPE,with a nondiagnostic V––PP scan, Dx. scan, Dx. should be rigorously pursuedshould be rigorously pursued

• nondiagnostic Vnondiagnostic V––PP scan :scan : with low with low probability or with moderate probability or with moderate probability but negativeprobability but negative D-dimer test D-dimer test , no additional testing or therapy, no additional testing or therapy is is indicatedindicated

Imaging StudiesImaging Studies -4 -4

• a recent study of 221 patientsa recent study of 221 patients with with susp. APE, MRI of the lung followed by susp. APE, MRI of the lung followed by MR venography ---successfully search MR venography ---successfully search for both DVT & PEfor both DVT & PE

• Echocardiography may reveal findings Echocardiography may reveal findings that strongly support hemodynamicallythat strongly support hemodynamically

significant PE, offering the potential tosignificant PE, offering the potential to

guide treatmentguide treatment

TreatmentTreatment

Anticoagulation-1Anticoagulation-1

• Bed rest is not recommended for DVT Bed rest is not recommended for DVT unlessunless substantial pain & swelling substantial pain & swelling

• PE diagnosed, inpatient therapyPE diagnosed, inpatient therapy with with initial bed rest for 24 to 48 hrs : often initial bed rest for 24 to 48 hrs : often recommendedrecommended

Anticoagulation-2Anticoagulation-2

• APE (+):IV anticoagulationAPE (+):IV anticoagulation with LMW with LMW heparin ,heparin , or standard, UF heparin should or standard, UF heparin should be initiated unless be initiated unless contraindicatedcontraindicated

• Not thrombolytic, but decreasing the Not thrombolytic, but decreasing the thromboembolic burdenthromboembolic burden

• If the suspicion of PE is high, parenteral If the suspicion of PE is high, parenteral anticoagulationanticoagulation should be considered should be considered even before imagingeven before imaging

Anticoagulation-3Anticoagulation-3

• Warfarin canWarfarin can be initiated on day 1 of be initiated on day 1 of therapytherapy

• SC LMWH or weight-based UFH IV should SC LMWH or weight-based UFH IV should be administered for at least 5 days until be administered for at least 5 days until INR=2.0 to 3.0 for 2 consecutive daysINR=2.0 to 3.0 for 2 consecutive days

• With standard heparin,aPTT checked Q6h With standard heparin,aPTT checked Q6h until it is =1.5 to 2.5 X controluntil it is =1.5 to 2.5 X control

• AchievingAchieving a therapeutic aPTT within 24a therapeutic aPTT within 24

hours ,reduce the risk of recurrencehours ,reduce the risk of recurrence

Anticoagulation-4Anticoagulation-4

• LMWHs have advantages over UFH : LMWHs have advantages over UFH : greater bioavailability, more predictablegreater bioavailability, more predictable

dosing, SC delivery, & a lower risk of dosing, SC delivery, & a lower risk of heparin-induced thrombocytopenia ( HIT )heparin-induced thrombocytopenia ( HIT )

• Monitoring LMWH by antiMonitoring LMWH by anti––factor Xafactor Xa : : morbidly obese (weighingmorbidly obese (weighing >150 kg) or >150 kg) or very small (<40 kg), pregnant,very small (<40 kg), pregnant, & very & very severe renal insufficiencysevere renal insufficiency or rapidly or rapidly changing renal functionchanging renal function

Anticoagulation-5Anticoagulation-5

• VTE require long-termVTE require long-term anticoagulation to anticoagulation to prevent extension & recurrenceprevent extension & recurrence

• Documented VTE with transientDocumented VTE with transient risk factors risk factors should treat 3 to 6 months, but more should treat 3 to 6 months, but more extendedextended treatment is appropriate when treatment is appropriate when significant risk factors persist, idiopathic or significant risk factors persist, idiopathic or previous episodesprevious episodes of VTEof VTE

• D-dimer levels may help guide decisions D-dimer levels may help guide decisions aboutabout the duration of therapythe duration of therapy

Anticoagulation-6Anticoagulation-6

• Tx. with a direct thrombin inhibitor (e.g., Tx. with a direct thrombin inhibitor (e.g., argatrobanargatroban or lepirudin) for HIT with or lepirudin) for HIT with thrombosisthrombosis

• Tx. with warfarin should not be initiatedTx. with warfarin should not be initiated

until disease process has been controlled until disease process has been controlled & platelet& platelet count has returned to the count has returned to the normal range---potentialnormal range---potential for worsening for worsening thrombotic complications :venous limbthrombotic complications :venous limb

gangrene & warfarin-induced skin necrosisgangrene & warfarin-induced skin necrosis

Placement of a Vena Caval Placement of a Vena Caval FilterFilter

• contraindications to anticoagulationcontraindications to anticoagulation

• major bleedingmajor bleeding during anticoagulationduring anticoagulation

• recurrent embolismrecurrent embolism under adequate under adequate therapytherapy

• filters are effective in reducing the filters are effective in reducing the incidence of PE, they increase the incidence of PE, they increase the subsequent incidence of DVT,but do subsequent incidence of DVT,but do not increase overall survivalnot increase overall survival

Treatment of Massive PETreatment of Massive PE

• PE causing hemodynamic instabilityPE causing hemodynamic instability

• resulting RV failure---compromised LV resulting RV failure---compromised LV preloadpreload

• If saline is infused for hypotension,If saline is infused for hypotension, it it should be done with cautionshould be done with caution

• Vasopressor therapy (e.g., dopamine)Vasopressor therapy (e.g., dopamine)

should be considered if BP is not should be considered if BP is not rapidly restoredrapidly restored

Complications of Thrombolytic Therapy-Complications of Thrombolytic Therapy-

11

• most widely accepted indication for most widely accepted indication for thrombolytic therapy :proven PE with thrombolytic therapy :proven PE with cardiogenic shock cardiogenic shock

• frequently considered :frequently considered : systemic systemic hypotension without shock hypotension without shock

• may be considered :may be considered : severely severely compromised oxygenation or a massive compromised oxygenation or a massive embolic burden identified by imageembolic burden identified by image

Complications of Thrombolytic Therapy-Complications of Thrombolytic Therapy-22

• The most devastating complication :ICHThe most devastating complication :ICH

• retroperitoneal & GI bleeding & bleeding retroperitoneal & GI bleeding & bleeding from surgical wounds or sites of recent from surgical wounds or sites of recent invasive procedures invasive procedures

• Contraindications : intracranial, spinal, or Contraindications : intracranial, spinal, or ocular surgery or disease, recent major ocular surgery or disease, recent major surgery or other invasive procedures, surgery or other invasive procedures, active or recent major bleeding, pregnancy, active or recent major bleeding, pregnancy, & clinically obvious risks of bleeding & clinically obvious risks of bleeding

PrognosisPrognosis

• The 3-month overall mortality :15 - 18% The 3-month overall mortality :15 - 18%

• Shock at presentation : increase in Shock at presentation : increase in mortality by a factor of 3 to 7mortality by a factor of 3 to 7

• post-thrombotic syndrome (chronic leg post-thrombotic syndrome (chronic leg pain & swelling) &pain & swelling) & chronic chronic thromboembolic pulmonary thromboembolic pulmonary hypertension :possible long-term hypertension :possible long-term sequelae of APEsequelae of APE

Prevention-1Prevention-1

Without prophylaxis, risk of VTE among Without prophylaxis, risk of VTE among acutely ill, hospitalized medical patients : acutely ill, hospitalized medical patients : as high as 15% as high as 15%

• Unfortunately, prophylaxis is grossly Unfortunately, prophylaxis is grossly underused ( U.S. & international studies )underused ( U.S. & international studies )

• Anticoagulant prophylaxis is more Anticoagulant prophylaxis is more effective than lower-limb mechanical effective than lower-limb mechanical prophylaxisprophylaxis

Prevention-2Prevention-2

• After total hip or knee replacement, After total hip or knee replacement, the risk of venous thrombosis : 50% the risk of venous thrombosis : 50% or higher without prophylaxis or higher without prophylaxis

• Trauma & spinal cord injury :also Trauma & spinal cord injury :also very-high-risk scenarios very-high-risk scenarios

• Every hospitalized patient should be Every hospitalized patient should be assessed for the need for prophylaxis assessed for the need for prophylaxis

Pregnancy & Acute Pregnancy & Acute Pulmonary EmbolismPulmonary Embolism

Pregnancy & APE-1Pregnancy & APE-1

• increased risk for VTE : pregnancy ,increased risk for VTE : pregnancy , postpartum period ,&postpartum period ,& hormone therapy hormone therapy

• Risk of a first episode of VTE= 5-fold as Risk of a first episode of VTE= 5-fold as high in the postpartum period as during high in the postpartum period as during pregnancy pregnancy

• Risk of PE = 15-fold as high during the Risk of PE = 15-fold as high during the postpartum period as during pregnancy postpartum period as during pregnancy

Pregnancy & APE-2Pregnancy & APE-2

• Low-dose oral contraceptives increase Low-dose oral contraceptives increase the risk of VTE : a factor of 2 to 5the risk of VTE : a factor of 2 to 5

• HRT increases the risk of VTE : a factor of HRT increases the risk of VTE : a factor of 2 to 42 to 4

• Pregnant patients with acute VTE require Pregnant patients with acute VTE require the same initial approach as other the same initial approach as other patients with regard to the need for patients with regard to the need for parenteral anticoagulation, placement of parenteral anticoagulation, placement of an IVC filter, or embolectomy an IVC filter, or embolectomy

ConclusionsConclusions

ConclusionsConclusions

• Untreated PE is associated with high Untreated PE is associated with high mortality mortality

• Suspected PE demands prompt Suspected PE demands prompt diagnostic testing & assessment of diagnostic testing & assessment of risk factors & clinical probability, with risk factors & clinical probability, with empirical clinical assessment & a empirical clinical assessment & a validated clinical prediction score validated clinical prediction score when possible when possible