Pulmonaryembolism ....tanmay new

Dr. TANMAY JAINResident , Chest MedicineGMC, NAGPUR

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GoalsUnderstand the historical context of pulmonary

emboli

Comprehend the pathophysiology and know some common risk factors

Be aware of the clinical features of PE and have a basic understanding of various diagnostic test

Gain a therapeutic approach to the treatment of PE and discuss a simplified method in the work-up of PE

Attempt to dispel a few “myths”about pulmonary emboli

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PerspectiveA Common disorder and potentially lethal

630,000 cases occurring annually with 2,00000 related deaths

Highest incidence in hospitalized patients

Autopsy reports suggest it is commonly “missed” diagnosed

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Perspective Presentation is often “atypical”

Signs and symptoms are frequently vague and nonspecific and rarely “classic”

Untreated mortality rate of 20% - 30%, plummets to 5% with timely intervention

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Historical ContextPre-1930’s

Heparin

Eugine Robin article (1977)

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Historical Context

PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) 1990

Published their data on the sensitivities and specificities of V/Q scans for PE.

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Why care????? PE is the most common preventable cause of death

in hospitalized patients ~600,000 deaths/year 80% of pulmonary emboli occur without prior

warning signs or symptoms 2/3 of deaths due to pulmonary emboli occur

within 30 minutes of embolization Death due to massive PE is often immediate Diagnosis can be difficult Early treatment is highly effective

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PathophysiologyRudolph Virchow, 1858

Triad: Hypercoagulability Stasis to flow Vessel injury

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Risk FactorsHypercoagulabilityMalignancy

Nonmalignant thrombophiliaPregnancyPostpartum status (<4wk)Estrogen/ OCP’s Genetic mutations (Factor V Leiden, Protein

C & S deficiency, Prothrombin mutations, anti-thrombin III deficiency)

Anti cardiolipin abNephrotic syndromeIBDPNHDICEssential thrombocytosis

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Venous Stasis Prior venous thrombosis Bedrest > 24 hr

Recent cast or external fixatorLong-distance travel or prolong automobile travel

CHF,

Vessel wall InjuryRecent surgery requiring endotracheal intubationRecent trauma (especially the lower extremities,head and pelvis)

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Natural History of VTE-(80%–95%) of PE occur as a result of

thrombus originating in the lower extremity.

40-50% of pts with DVT develop PE, often “silent”

PE presents 3-7 days after DVTFatal within 1 hour after onset of respiratory

symptoms in 10%Shock/persistent hypotension in 5-10% (up to

50% of patients with RV dysfunction)Most fatalities occur in untreated pts

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Clinical Presentation The Classic Triad: (Hemoptysis, Dyspnea,

Pleuritic Pain)

Not very common! Occurs in less than 20% of patients with

documented PE Syncope=rare presentation, but indicates

severely reduced hemodynamic reserve

In pts with pre-existing CHF or COPD, worsening dyspnea may indicate PE

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Three Clinical Presentations

Pulmonary Infarction -have pleuritic chest pain

Submassive Embolism

Massive Embolism -a clot which obstructs two lobar arteries, so-called “Saddle Embolus”. Acute cor pulmonale

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Mythology of PEMyth

“Patients with pulmonary embolism are short of breath and have chest pain!”

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Clinical Features Symptoms in Patients with Angio Proven

PTE

Symptom Percent

Dyspnea 84Chest Pain, pleuritic 74Anxiety 59Cough 53Hemoptysis 30Sweating 27Chest Pain, nonpleuritic 14Syncope 13

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Clinical Features Signs with Angiographically Proven PE

Sign Percent

Tachypnea > 20/min 92Rales 58Accentuated S2 53Tachycardia >100/min 44Fever > 37.8 43Diaphoresis 36S3 or S4 gallop 34

Thrombophebitis 32Lower extremity edema 24

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Who do we work up?-

Transition from tech oriented approach to bayesian analysis.

Pretest Probability

Helps in the selection and interpretation of futher diagnostic tests to create a post test probablity

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Ingredients for a Proper Dx

Clinical Suspicion,Signs and SxsRisk FactorsLab Tests

IMAGING21

Diagnostic Test Imaging Studies

CXR V/Q ScansHRCT MRICTPAPulmonary Angiography EchocardiograpyDuplex USG

Laboratory Analysis CBC, ESR, Hgb/Hct, D-Dimer ABG’s

Ancillary Testing EKG Pulse Oximetry

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Diagnostic Testing- CXR’s

Chest X-Ray Myth:

“You have to do a chest x-ray so you can find Hampton’s hump or a Westermark sign.”

Reality:

Most chest x-rays in patients with PE are nonspecific and insensitive

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Diagnostic Testing - CXR’s

Chest radiograph findings in patient with pulmonary embolism

CardiomegalyNormal studyAtelectasis Elevated HemidiaphragmPulmonary Artery EnlargementPleural EffusionParenchymal Pulmonary Infiltrate

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Chest X-ray Eponyms of PEWestermark's sign

A dilation of the pulmonary vessels proximal to the embolism along with collapse of distal vessels, sometimes with a sharp cutoff.

Hampton’s Hump

A triangular or rounded pleural-based infiltrate with the apex toward the hilum, usually located adjacent to the hilum.

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Westermark’s Sign

Hampton’s Hump

Diagnostic Testing – EKG’s

EKG

Most Common Findings:

Tachycardia or nonspecific ST/T-wave changes

Acute cor pulmonale or right strain patterns

Tall peaked T-waves in lead II (P pulmonale) Right axis deviation RBBB S1-Q3-T3 (specific but occurs in only 20% of PE

patients)(Last three in V1-V3 suggests RV dysfunction)

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S1Q3T3 & T wave changes

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Duplex USGMain criteria used is non compressibility of a

venous segment.

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Diagnostic Testing - Pulse Oximetry

The Pulse Oximetry Myth:

“ You must do a pulse oximetry reading, since patients with pulmonary embolism are hypoxemic!”

Reality:

Most patients with a PE have a normal pulse oximetry, and most patients with an abnormal pulse oximetry will not have a PE.

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Diagnostic Testing - ABG’s

The ABG/ A-a Gradient myth:

“You must do an arterial blood gas and calculate the alveolar-arterial gradient. Normal A-a gradient virtually rules out PE”.

Reality:

The A-a gradient is a better measure of gas exchange than the pO2, but it is nonspecific and insensitive in ruling out PE.

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Diagnostic TestingEchocardiography

Consider in every patient with a documented pulmonary embolism EKG maybe helpful in demonstrating right heart

strain

Early fibrinolysis can reduce mortality 50%!

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D-dimer TestFibrin split product

Circulating half-life of 4-6 hours

Quantitative test have 80-85% sensitivity, and 93-100% negative predictive value

False Positives:

Pregnant Patients Post-partum < 1 weekMalignancy Surgery within 1 weekAdvanced age > 80 years SepsisHemmorrhage CVAAMI Collagen Vascular

DiseasesHepatic Impairment

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Diagnostic TestingD-dimer

Qualitative Bed side RBC agglutination test

“SimpliRED D-dimer”

Quantitative Enzyme linked immunosorbent asssay “Dimertest” Positive assay is > 500ng/ml VIDAS D-dimer, 2nd generation ELISA test

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Ventilation/Perfusion Scan- “V/Q Scan”

A common modality to image the lung and its use still stems from the PIOPED study.

Relatively noninvasive and sadly most often nondiagnostic

In many centers remains the initial test of choice

Preferred test in pregnant patients, renal dysfunction

50 mrem vs 800mrem (with spiral CT)

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Ventilation-perfusion scintigraphy

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Right upper lobe: „match”, Both lower lobes: „mismatch

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Interpretation Normal Low probability/”nondiagnostic” (most common) High Probability

Simplified approached to the interpretation of results:

High probability Treat for PENormal Scan If low pre-test, your doneEverything else Purse another study (CT, Angio)

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Spiral (Helical) Chest CTAdvantages

Noninvasive and RapidAlternative Diagnosis

Disadvantages

Risk to patients with borderline renal functionHard to detect subsegmental pulmonary

emboli

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At the present time, CT can be consideredconfirmatory in excluding embolism in patients with a low or intermediate likelihood of disease andconfirming embolism in patients with intermediate or high probability of disease. When discordanceexists between the clinical assessment and CT findings, additional studies should be considered.

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Pulmonary Angiography

“Gold Standard”Performed in an Interventional Cath Lab &

invasive. It requires expertise in study, performance &

interpretation.

Positive result is a “cutoff” of flow or intraluminal filling defect

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CT-PAFirst line investigation at present.Widespread use has resulted in the over

diagnosis of PE, i.e clinically insignificant disease

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Current diagnostic strategies capable of excluding diagnosis of PE

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Current diagnostic strategies capable of confirming diagnosis of PE

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Treatment:

Goals: Prevent death from a current embolic

event

Reduce the likelihood of recurrent embolic events

Minimize the long-term morbidity of the event

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Dr. Batizy explaining the CT results

When a diagnosis of venous thromboembolism is suspected, empiric treatment should be considered until the diagnosis is either objectively excluded or confirmed.

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TreatmentAnticoagulants

Heparin Provides immediate thrombin inhibition, which

prevents thrombus extension & embolic recurrence

Does not dissolve existing clot

Will not work in patients with antithrombin III def. In this case use hirudins

Few absolute contraindications

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TreatmentAnticoagulants

Heparin Available as Unfractionated or LMW Heparin

FDA approved dosing:

Unfractionated: 80 units/kg bolus, 18 units/kg/hr

LMWH: 1 mg/kg every 12hr or 1.5mg/kg per Day

LMWH (Lovenox) prefered in pregnant patients

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Fixed dose of s/c UFH without aPTT monitoring, as an initial dose of 333 U/kg f/b 250 U/kg every 12 hours, has been demonstrated to be as safe and effective as LMWH in patients presenting with DVT and PE.

LMWH v/s UFH Enoxaparin, Tinzaparin , Nadroparin ,

Dalteparin50

FONDAPARINUXSelectively binds factor Xa and inhibits

thrombin generation.T1/2 17 hrs- renal excr.Approved for prophylaxis before major sx and

for t/t of DVT & PE in conjuction with warfarin.

Rivaroxaban is oral factor Xa inhibitor

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Direct thrombin inhibitorsLepirudin, Argatroban- synth polysacchrides.T1/2 40-60 mins, i/v infusion, monitering with

aPTT.Approved for t/t of VTE due to heparin IT.

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Thrombolysis therapy Indications:

Documented PE with: Persistent hypotension Syncope with persistent hemodynamic compromise Significant hypoxemia +/- patient with acute right heart strain

FDA Approved –Alteplase, STK, Urokinase, regimen is 100mg as a continuous IV infusion. PEITHO( PE Thrombolysis trial) – for saftey & efficacy

of Tenectiplase

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TreatmentEmbolectomy

Prefibrinolytic therapy this was only therapy for massive PE

Carries a 40% operative mortality

Last resort for pts with persistant hypotension,shock who failed thrmbolysis or C/I.

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Interventional thrombus fragmentationWide variety of devices that use pressured

saline and rotating impellers to break central thrombus.

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Long term managmentRecurrence commonAnticoagulants

Warfarin (Coumadin) Vit k antagonist

Requires 3-5 days to acieve full therapeutic effecacy

Important a patient is anticoagulated with heparin before initiating warfarin therapy

Target INR is 2.0 – 3.0

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Side effects- bleeding teratogenic cholesterol microembolismDose – 5mg or 10 mg at the start with

adjustment acc to INR

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Novel agents for long term m/m1.Dabigatran-oral direct thrombin inhibitor2.Apixaban3.Aspirin – reduces major vascular events

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VENA CAVA INTERRUPTION AND VENA CAVA FILTER IVC filter placement is to prevent PE in

patients who have a contraindication to anticoagulation

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CTEPH Residual thromboembolic burden is

sufficiently extensive to cause CTEPH 0.5% to 3.8% in initial episode of PE to

13.4% following recurrent episodes of VTE Pulmonary thromboendarterectomy, which

involves the dissection of endothelialized thrombi under cardiopulmonary bypass and deep hypothermia.

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PROPHYLAXISUFHLMWH (enoxaparin, dalteparin)Factor Xa inhibitors (fondaparinux,

rivaroxaban) WarfarinWhen administered correctly in appropriate

patients, its safe and effective with an absolute reduction in the incidence of VTE in the range of 40% to 60%.

Major bleeding complications occur in less than 1% of patients

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ConclusionSummary Points

Pulmonary Emboli remain a potentially deadly and common event which may present in various ways

Don't’ be fooled if your patient lacks the “classic” signs and symptoms!

Consider PE in any patient with an unexplainable cause of dyspnea, pleuritic chest pain, or findings of tachycardia, tachpnea, or hypoxemia

2nd Generation Qualitative D-Dimers have NPV of 93-99%

Heparin remains the mainstay of therapy with the initiation of Warfarin to follow

Simplified Algorithm: ( Pretest probability, D-Dimer, +/- CT angio)

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Thank you

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