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Pulmonary Embolism

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Outline of Lecture

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 PaO2 less than 80 (75%)

PaO2 is very sensitive to minute ventilation

1-2 breaths/ minute may normalize the PaO2

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

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)

 

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

 

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

“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

  • 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:
    • Fibrinolytics should be given if PE is confirmed
    • Heparin should be started immediately since PE is strongly suspected
    • Enoxaparin is a better choice for anticoagulation since it has better Xa:IIa ratio
    • Fibrinolytics should be considered only if RV strain/dysfunction demonstrated
    • 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:

 

  • Treat for PE only if the D-Dimer is greater than 500 ng/mL
  • Pregnancy is an absolute contraindiaction to fibrinolytics
  • Heparin should be started after obtaining imaging studies that confirm VTE or PTE
  • A negative Quantitative ELISA D-Dimer rules out PE
  • A V/Q scan is the study of choice
  • Helical CTPA is not contraindicated
  • 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.

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

Questions

4.  Which of the following statments is correct:

  • Heparin exerts its effects on Factors II,VII, IX,X, protein C, protein S
  • Lovenox has greater factor IIa effect than heparin
  • An INR of greater than 3 is theraputic in patients with hypercoagulability states
  • Fibrinoltics should be given concominately with heparin
  • Aspirin should be given to patients with PE
  • 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:

  • Antibiotics given empirically
  • Heparin should be started prior to imaging studies since PE is high on the differential
  • Fibrinolytics should be given due to unstable status
  • CT Angio prior to starting heparin
  • Budd-Chiari is not on the differential

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