Pulmonary Embolism

Jeff Curly Hurley MD Martin Luther King Jr. Hospital Charles Drew University

Objectives

     Perspective – Are pulmonary embolisms bad?

Presentation – “I think I’m having a PE” Diagnosis – Anxiety Treatment – Now and Later Questions – Designed to wreak havoc

Perspective

   Leading cause of Morbidity and Mortality Estimated at 780,000 deaths per year Difficult diagnosis to make – In patients suspected of having the disease, approximate 10-20% are positive – Approximate 66% of PE cases are missed.

– Conversely, 62% of patients on anticoagulation therapy for suspected PE and subsequently died, no PE was found on autopsy

DVT to PE

  Diagnosis of DVT – 600,000 hospitalizations – Diagnosis is underestimated Diagnosis of PE – 400,000 missed each year – Mortality if untreated is 20-30% – Mortality if treated is 2-10% – 100,000 potential lawsuits – Cardiac arrest (PEA): TEE demonstrated 36% prevalence rate for PE

Vichow’s Triad

 Hypercoagulability  Endothelial damage  Stasis

Thromboembolism Risk Factors

          Age > 40 (old age in Rosen’s) History of venous thromboembolism Surgery longer than 30 minutes Prolonged immobilization (airplanes—ASA) CHF Cancer Obesity Pregnancy or recent delivery Hormone replacement therapy Hypercoagulable states

Thromboembolism Risk Factors

 Hypercoagulable states – Factor V Leiden (Most common) – AT III deficiency – Protein C deficiency – Protein S deficiency – Prothrombin G20210A mutation – Anticardiolipin antibody syndrome – Lupus anticoagulant

      

DVT

Homans’ and pseudo-Homans’ – Pseudo-Homans’: tenderness when squeezing the calf – Homans’: Foot held in plantar flexation – Repudiated by Homan himself Classic physical findings present – Only 50% have DVT Plegmasia Dolens – White, painful, edematous, cold, and pulseless – Limb threat—call vascular—or amputation required Approx. 60-80% of femoral, and 30-45% of calf DVT’s embolize Only half of patients with a proven PE have U/S evidence of a DVT – Negative ultrasound does not exclude PE DVT may mimic cellulitis Axillary/Subclavian veins highest risk

PE

    Massive PE is one of the most common causes of unexpected death 10% of patients in whom acute PE is diagnosed die within the first 60 minutes Recurrent PE / development of pulmonary hypertension / chronic cor pulmonale – occurs in up to 70% of patients – Has a high mortality and morbidity PE is especially likely to be missed in older patients

Presentation

  Typical – Pleuritic chest pain – Dyspnea – Hypoxia Non typical – Apprehension – Cough – Hemoptysis – Sweating – Non-Pleuritic chest pain – Syncope

Presentation

  Classical Triad – Chest pain, Dyspnea, Hemoptysis < 20% – Dyspnea, Tachypnea, or Chest Pain--97% Other Symptoms – Dyspnea (73%) – Tachypnea (70-92%) – Pleuritic chest pain (66%) – Tachycardia (44%) – Rales (58%) – Temperature > 100 (43%) – Leg Pain (26%) – Tenderness on chest wall palpation is common

Differential Diagnosis

     Pneumonia – PE in Patients with pneumonia is virtually always missed Asthma – Bronchospasm on PE responds to asthma meds – 50% of patients that die from Asthma have a different diagnosis on autopsy Pleuritis – rarely the correct diagnosis ACS/MI – High level of confusion between PE and MI in patients with impending arrest Carcinoma

Pursuing the Diagnosis

  General Rule: – Whenever the patient has risk factors and symptoms suggesting PE, and no other reasonable diagnosis – Shortness of breath is the most common complaint associated with unexpected death after ED discharge Clinical Suspicion (PIOPED): – Intermediate clinical suspicion 64% – High suspicion: 68% correct – Low Suspicion: 91% correct

Work-Up

 Clinical evaluation  EKG  CXR  ABG  D-Dimer  V/Q scan  CTPA

Initial Studies

  Chest x-ray to R/O: – PTX, PNA, CHF, CM, Dissection Findings suggestive of PE – Focal infiltrates/atelectasis (68%) – Elevated hemidiaphragm (24 50%) – Pleural effusion (48%) – Prominent Pulm. Arteries – Hampton’s hump (35%) – Westermark’s sign (7%)   ECG to R/O: – ACS/Pericarditis/Strain -prognostic ECG – S1Q3T3 (indication

of right heart strain— 20-50%)

– ST-segment changes (8-69%) – Non-specific ST-T wave changes (49-77%) – RBBB (6-67%) – T-Wave inversions (23 64%) – Atrial arrhythmias (3 66%) – Normal (9-30%)

Hampton’s Hump

Westermark

S1Q3T3

ABG

        ABG has zero predictive value A-a Gradient is often increased secondary to other pulmonary pathology Gradient is usually about 15 in most patients PE does not often produce abnormalities in gas exchange Most patients have a PaO 2 less than 80 (75%) PaO 2 is very sensitive to minute ventilation – 1-2 breaths/ minute may normalize the PaO 2 Pulse ox often normal (100% tends to exclude PE) PIOPED Data: – Low Sensitivity – 14-38% of patients with normal ABG had PE

Pre-Test Probability For DVT

Clinical Probability: Wells

 Wells Criteria

Variable Points

HR > 100 1.5

Hx of DVT/PE 1.5

Pretest Probability

Low < 2 Moderate = 2 to 6 High > 6 Immobilization Hemoptysis Malignancy Symptoms of DVT PE more likely 1.5

1 1 3 3

D-Dimer

  34- D-Dimer assays with varying degrees of sensitivity – ELISA assays: highly sensitive (95-99%), expensive  Original tests were slow to be of value – Run in batches/Highly skilled lab/Impractical in the ER  Now rapid ELISAs are available with similar sensitivities – Latex agglutination: 85%-98% – Quantitative is gold standard D-Dimer Test: Considered positive if greater tan 500 ng/ml – A positive D-Dimer does not meet the requirements for an intent to treat Lower sensitivity (latex and whole blood) D-Dimer insufficient to r/o PE ALONE – ACEP Recommendations: in conjunction with Well’s

D-Dimer



NEJM: D- Dimer only used in

patients who are low risk for PE  High D-Dimer is meaningless – Not established a diagnosis  Side Note: D-Dimer not necessary/not helpful for DIC diagnosis – Platelet trend, FSP/FDP, Fibrinogen level, PT/PTT

D-Dimer

    Half-life is 8 hours Patients with symptoms of PE greater than 8 days Patients may have normally elevated D Dimers – Pregnant patients (75%) – Cancer patients (50%) – Postpartum 1 week – Age greater than 80 Other disease processes: – Sepsis, hemorrhage, MI, stroke, collagen vascular diseases, liver disease

Statistics

   

Sensitivity: ill

– A/(A +B)

Specificity: well

– D/(C + D)

Positive Predictive Value

– A/(A +C)

Negative Predictive Value

– D/(B + D) Test Positive Test Negativ e Disease Present Disease Absent A C B D

V/Q scan

   PIOPED data show that the specificity is poor – Normal V/Q scans—did angiogram—9% positive for PE High-probability scan sensitivity of 41% and specificity of 97% 65% of V/Q scans are interpreted as low and intermediate scans which generally requires further investigation

Spiral CT Scan

    Highly sensitivity: 98-99% Safe British Thoracic Society: recommendation that CTPA is the initial lung imaging study for suspected PE NEJM: – Positive Helical CT: anticoagulation – Negative Helical CT: possible F/U with compression ultrasound then possible anticoagulation

Special Populations

  Recurrent visits in Pts. with diagnosed PE – INR: if therapeutic (INR 2-3), no imaging – NEW symptoms suggestive of recurrent PE: use the same imaging modality Massive Obesity – Greater than 400 lbs – CT, V/Q, Angiogram: not feasible – Venous ultrasound – D-Dimer: greater than 2000—treat (no evidence backing this recommendation— Tintinalli’s)

Special Populations

  Pregnancy – Involve obstetrician and radiologist – Half dose injection V/Q scan – CT angiogram – Quantitative D-Dimer should not exceed 1000 ng/mL – Doppler ultrasound Hypercoagulability – May require higher INRs to be therapeutic ( >3) – May render heparin and LMWH ineffective

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ACEP Recommendations

Level B recommendation that a quantitative D-dimer excludes PE or lower extremity DVT in low pre-test probability patients (as assessed either subjectively or by clinical scores). Level B recommendation that a negative whole blood D-dimer assay in a low pre-test probability patient as assessed by the Wells criteria excludes PE or lower extremity DVT There was insufficient evidence to make any Level B recommendations in regard to utilizing the whole blood qualitative D-dimer assay without Well's clinical scoring system.

ACEP Recommendations

 1.

2.

3.

4.

"In patients with a low-to-moderate pretest probability of PE, and a non-diagnostic V/Q scan, use one of the following tests instead of pulmonary arteriogram to exclude clinically significant PE: A negative quantitative D-dimer assay (turbidimetric or ELISA). A negative whole blood cell qualitative D-dimer assay in conjunction with a Wells [PE] score of four or less. A negative single bilateral venous ultrasonographic scan for low-probability patients. A negative serial bilateral venous ultrasonographic scan for moderate probability patients."

ACEP Recommendations

 PE policy Level B recommendation states, "Consider fibrinolytic therapy in hemodynamically unstable patients with confirmed PE." The Level C recommendation states, "Consider fibrinolytic therapy in hemodynamically stable patients with confirmed PE and RV dysfunction on echocardiography," and, in unstable patients with high clinical index of suspicion, especially if RV dysfunction can be demonstrated on bedside echocardiography.

Treatment

– Anticoagulation:    Prevent recurrent thromboembolism (rate new PE is 23% in 24 hours versus 6% in treated patients— therapeutic aPTT) Started if suspected (pretest probability > 50%) confirmed PE Can always stop Heparin Drip – Unfractionated Heparin:       Dose 80 U/kg Bolus, 18 U/kg infusion.

– Rosen’s: 60% of patients not therapeutic with

this dosing in the first 24 hours—recommend 100-150 Unit/Kg dosing

Usually 5,000-10,000 U bolus (Rosen’s—10K start) PTT 60-80 Effective anticoagulation has been shown to reduce the overall mortality rate from 30% to less than 10% Heparin should be started as soon as the diagnosis of pulmonary thromboembolism is considered seriously 15 mg of protamine sulfate reverses anticoagulant effect

Treatment

  Low Molecular Weight Heparin: – 612 Patients (308 Heparin, 304 LMWH) – No difference in mortality, recurrence, bleeding (NEJM) – More effective anticoagulation—Better Xa:IIa ratio – Less side effects – Dose is 1 mg/Kg Q12 or 1.5 mg/Kg Daily – Max Dose is 250 mg/day – “In May 1998, LMWH (Enoxaparin, Rhone-Poulenc Rorer, Collegeville, PA) was deemed approvable by the Food and Drug Administration for in- and outpatient treatment of DVT and PE and extended use of LMWH for outpatient treatment of DVT and PE.“ – 1mg Protamine sulfate reverses 1 mg Lovenox Warfarin – Goal of INR 2-3 – INR greater than 2.5 according to Rosen’s

HAT

 Heparin-Associated Thrombocytopenia occurs in 4% of patients – 2/3 of these patients will not have a reaction to LMWH – If HAT occurs, heparin must be stopped immediately  Diagnosed by disseminated thrombosis acutely  Or by a falling platelet count over time – Drug of Choice if HAT occurs is lepirudin  Hirudins are direct inhibitors of Thrombin – Lepirudin also DOC for AT III deficiency

Coagulation Cascade

Treatment

  Supportive: – IVF – Oxygen  Even when PaO2 is normal—may dilate pulm. vasculature – Pain control  Morphine: pulmonary vasodilator Shock: – Fluid Boluses – Volume expansion may not beneficial: actually will increase RV afterload and worsen RV function – Shock should be treated with norepinephrine (Rosen’s) – Fibrinolytics indicated: expected mortality decrease of 50%

Fibrinolysis

  Fibrinolytics/Surgery in cardiopulmonary arrest – CPR has no benefit (36% of PEAs) – Emergency cardiopulmonary bypass (one study that showed 7 out of 9 patients survived) – Bilateral emergency thoracotomy and massage of the pulmonary vasculature – Patient with known PE in ED or in transfer to the ED has Arrest—give alteplase 100 mg bolus then CPR x 20 minutes Fibrinolytics indicated in: – Cardiogenic shock – RV Failure either by ECHO or strain on EKG – Prior history of PE or known Protein C, Protein S, AT III deficiencies (emedicine) (patients with high likelihood for recurrences)

Fibrinolysis

   

Indicated for iliofemoral DVT

– Call intervential radiologist Complications of fibrinolytics – ICH bleeding 2% – Bleeding 20% “Fibrinolysis should be considered for all patients with PE who lack specific contraindications to the therapy. Many centers now regard fibrinolysis as the primary treatment of choice for all patients with PE and even for all patients who have DVT without evidence of PE” (emedicine) “Fibrinolysis is always indicated for hemodynamically unstable patients with PE, because no other medical therapy can improve acute cor pulmonale quickly enough to save the patient's life” (emedicine)

Fibrinolytics

  Reteplase: second generation – FDA has not approved reteplase for use in PE – Works faster – More effective against larger clot burden – Allows more clot dissolution – 10 unit IVP Q30min X2 – Arrest: single 20 unit IVP Alteplase: Drug most commonly used in the ED – Approved by FDA for use in PE – 100 mg IV infusion over 2 h – Accelerated 90-min regimen, most authors believe it is both safer and more effective than 2-h infusion (emedicine) 

Weight based

– Turn off heparin during infusion – Aspirin Contraindicated

Bleeding Complications

 Reversal with FFP – Usually 2 units  Reversal with epsilon-aminocaproic acid – Amicar: 4-5 gms PO/IV over 1 hour then 1 gm/hour as needed

Algorhythm

Consultations

  Decision to treat with thrombolytics – Solely the responsibility of the ER doctor Interventional Radiology – Catheter directed thrombolytics in selected patients – Placement of IVC filter – Possible treatment of DVTs  Rrosen’s: catherter-associated venous thrombosis and for non-catheter related – Decrease recurrence rate of DVT by 50% – Decrease crippling postphelbitic syndrome by 70%

Pitfalls: emedicine

– Dismissing complaints of unexplained shortness of breath as anxiety or hyperventilation without an adequate workup – Dismissing complaints of unexplained chest pain as musculoskeletal pain without an adequate workup – Failure to properly diagnose and treat symptomatic DVT – Failure to recognize that DVT below the knee is just as serious as more proximal DVT – Failure to order a V/Q scan when a patient has symptoms consistent with PE – Failure to pursue the diagnosis after a V/Q scan that is not perfectly normal – Failure to start full-dose heparin at the first real suspicion of PE, before the V/Q scan – Failure to give fibrinolytic therapy immediately when a patient with PE becomes hemodynamically unstable

References

    Marx, John MD, et al., Rosen's Emergency Medicine: Concepts and Clinical Practice, 5th ed, Mosby, 2002.

Tintinalli, Judith MD, et al., Emergency Medicine:A Comprehensive Study Guide, 6th ed, McGraw-Hill, 2002.

Feied, Craig MD, Pulmonary Embolism, Emedicine.com, December 13, 2002.

Nordenholz, Kristen MD, et al., Diagnostic Strategies for Pulmonary Embolism, Emergency Medicine, Vol. 36/Number 5, May 2004.

Questions

1.

33 year old male with PMH of AT III deficency c/o chest pain, left sided, pressure 4/10 radiating to the shoulder x 30 min. no associated/alleving factors. HR 105, RR 24, BP 140/80. Which of the following is true for this patient: 1. Fibrinolytics should be given if PE is confirmed 2. Heparin should be started immediately since PE is strongly suspected 3. Enoxaparin is a better choice for anticoagulation since it has better Xa:IIa ratio 4. Fibrinolytics should be considered only if RV strain/dysfunction demonstrated 5. TNKase is the drug of choice

Answer

  Fibrinolytic therapy is mandatory for 3 groups of patients: those who are hemodynamically unstable, those with right heart strain and exhausted cardiopulmonary reserves, and those who are expected to have multiple recurrences of pulmonary thromboembolism over a period of years. Patients with a prior history of PE and those with known deficiencies of protein C, protein S, or antithrombin III should be included in this latter group. Besides those for whom it is mandatory, fibrinolysis should be considered as a potential therapy for every patient with proven PE. – Emedicine.com

Questions

2. A 34 year old obese G4 P3 female at 36 weeks pregnancy and has a broken ankle complains of shortness of breath and pleurtic chest pain x 30 minutes. This has never happened in her previous pregnancies. Which of the following is true: 1. Treat for PE only if the D-Dimer is greater than 500 ng/mL 2. Pregnancy is an absolute contraindiaction to fibrinolytics 3. Heparin should be started after obtaining imaging studies that confirm VTE or PTE 4. A negative Quantitative ELISA D-Dimer rules out PE 5. A V/Q scan is the study of choice 6. Helical CTPA is not contraindicated 7. Negative serial bilateral venous ultrasonographic scan rules out PE

Questions

3. A 45 year old female Complains of Chest pain. A work up of PE is started. Data: CXR: infiltrate in RLL EKG: NSR at 95 with RBBB and inferior flipped Ts in II and III, ABG A-a gradient is 10, WBC of 12, Cr 2.1, PT/PTT of 12/80.

1. Alteplace and aspirin should be given if PE on CT since there is evidence of right heart strain 2. The A-a gradient rules out PE 3. Patient does not need anticoagulation 4. D-Dimer should be ordered regardless of pretest probability 5. Pneumonia is not in the differential 6. Patient has an autoimmune disease

Questions

4. Which of the following statments is correct: 1. Heparin exerts its effects on Factors II,VII, IX,X, protein C, protein S 2. Lovenox has greater factor IIa effect than heparin 3. An INR of greater than 3 is theraputic in patients with hypercoagulability states 4. Fibrinoltics should be given concominately with heparin 5. Aspirin should be given to patients with PE 6. Lepirudin is the first line treatment for Protein C and Protein S deficiency

Questions

5. 35 year old male c/o R leg pain and swelling, new onset chest pain x 30 minutes, and shortness of breath. On exam the patient is afebrile, tachycardic, tachypnic, hypotensive. Patient has scleral icterus, crackles in the RUL, bilateral pedal edema R>L and a positive Homan’s sign and a positive psuedo-Homan’s sign. Which statement acurately reflects this patients condition: 1. Antibiotics given empirically 2. Heparin should be started prior to imaging studies since PE is high on the differential 3. Fibrinolytics should be given due to unstable status 4. CT Angio prior to starting heparin 5. Budd-Chiari is not on the differential

UGH!