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
