Goals

1. Goals Understand 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 1 So let us beginSo let us begin

2. Perspective A common disorder and potentially deadly 650000 cases occuring annually Highest incidence in hospitalized patients Autopsy reports suggest it is commonly �missed� diagnosis

3. 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 3 PE It has a wide spectrum of patient presentation, which leads us to do suboptimal testing. This can stand in the way of a timely diagnosis It�s important, because prompt diagnosis and treatment can dramatically reduce the mortality rate and morbidity of this disease. Unfortunately, the diagnosis is missed far more than it is made. I want to offer you a historical perspective of the disorderPE It has a wide spectrum of patient presentation, which leads us to do suboptimal testing. This can stand in the way of a timely diagnosis It�s important, because prompt diagnosis and treatment can dramatically reduce the mortality rate and morbidity of this disease. Unfortunately, the diagnosis is missed far more than it is made.

4. Historical Context Pre-1930�s Heparin 4 Until the 1930�s, PTE was viewed almost universally fatal, with surgery the only treatment despite an operative mortality of 100% Enter heparin, circa 1930�s, heparin was discovered and its wide spread use were so immediate and dramatically apparent that this become the mainstay of treatment for the next 70 years! In 1977, a physician be the name of Eugene Robin published a landmark article which stimulated immense change in medicines approach to diagnosing PE. It was robin contention the while lung scintigraphy was sensitive to the presence of clots, but also non-specific. He questioned the value of ventilation scans when the perfusion defects were small. He felt angiography was being underused, and that PE�.was being OVER diagnosed. Until the 1930�s, PTE was viewed almost universally fatal, with surgery the only treatment despite an operative mortality of 100% Enter heparin, circa 1930�s, heparin was discovered and its wide spread use were so immediate and dramatically apparent that this become the mainstay of treatment for the next 70 years! In 1977, a physician be the name of Eugene Robin published a landmark article which stimulated immense change in medicines approach to diagnosing PE. It was robin contention the while lung scintigraphy was sensitive to the presence of clots, but also non-specific. He questioned the value of ventilation scans when the perfusion defects were small. He felt angiography was being underused, and that PE�.was being OVER diagnosed.

5. Historical Context PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) The Electronic Era, 2000 and Beyond� 5 Jump ahead to 1990. The PIOPED investigators, stimulated by Robins article published their data on the sensitivities and specificities of V/Q scans for PE. In summary, a random sample of 933 of 1493 patients were studied prospectively. 931 had scintography and 755 underwent angiography. Their conclusion: clinical assessment combined with the V/Q scan can establish the diagnosis or exclusion of pulmonary embolism only for a minority of patients Enter the electronic era, Craig Feied, MD, who has read every published article about PE written in the last 100 years and who has written the chapter in Rosen�s in the last two editions published this statement: Massive PE is one of the most common causes of unexpected death, being second only to coronary artery disease as a cause of sudden unexpected natural death at any age. Most clinicians do no appreciate the extent of the problem, because the diagnosis is unsuspected until autopsy in approximately 80% of cases. Jump ahead to 1990. The PIOPED investigators, stimulated by Robins article published their data on the sensitivities and specificities of V/Q scans for PE. In summary, a random sample of 933 of 1493 patients were studied prospectively. 931 had scintography and 755 underwent angiography. Their conclusion: clinical assessment combined with the V/Q scan can establish the diagnosis or exclusion of pulmonary embolism only for a minority of patients Enter the electronic era, Craig Feied, MD, who has read every published article about PE written in the last 100 years and who has written the chapter in Rosen�s in the last two editions published this statement: Massive PE is one of the most common causes of unexpected death, being second only to coronary artery disease as a cause of sudden unexpected natural death at any age. Most clinicians do no appreciate the extent of the problem, because the diagnosis is unsuspected until autopsy in approximately 80% of cases.

6. So What Do We Do ??? Confusing for Emergency Physician Do we under diagnose/over diagnose? Why don�t we have a standardized method of work up after all these years? 6 Do we under diagnose or over diagnose? If we over diagnose, is it such a big deal? It�s just a few month of inconvenience of heparin and warfarin. Aside from the potential morbidity of the anticoagulants,there are other problems. The diagnoses carries a stigma which will contaminate all future medical encounters. Women may be barred from oral contraceptives, future pregnancies will be considered high risk. Elective surgery may be denied. So, really after all these years, we are still left in the dark. We still don�t have a collective conscience on a standard approach to this problem. Before we can answer any questions we have to understand the condition and this take us to virchow. Do we under diagnose or over diagnose? If we over diagnose, is it such a big deal? It�s just a few month of inconvenience of heparin and warfarin. Aside from the potential morbidity of the anticoagulants,there are other problems. The diagnoses carries a stigma which will contaminate all future medical encounters. Women may be barred from oral contraceptives, future pregnancies will be considered high risk. Elective surgery may be denied. So, really after all these years, we are still left in the dark. We still don�t have a collective conscience on a standard approach to this problem. Before we can answer any questions we have to understand the condition and this take us to virchow.

7. Etiology Rudolph Virchow, 1858 Triad: Hypercoagulability Stasis to flow Vessel injury 7 Everyone I�m sure is familiar with Virchow�s triad. It was first described by this German pathologist. If we think of risk factors, we should think of them as the embodiment of the triad: hypercoagulability, stasis, and vessel injury. So, essentially, under normal conditions, microthrombi are continually formed and lysed with the venous circulatory system. When any one of the �risk states� exists, potential microthrombi may escape the normal fibrinolytic system and grow and propagate. Pulmonary Emboli occurs when fragments of thrombus break loose and are carried through the right side of the heart into the pulmonary arterial tree. Everyone I�m sure is familiar with Virchow�s triad. It was first described by this German pathologist. If we think of risk factors, we should think of them as the embodiment of the triad: hypercoagulability, stasis, and vessel injury. So, essentially, under normal conditions, microthrombi are continually formed and lysed with the venous circulatory system. When any one of the �risk states� exists, potential microthrombi may escape the normal fibrinolytic system and grow and propagate. Pulmonary Emboli occurs when fragments of thrombus break loose and are carried through the right side of the heart into the pulmonary arterial tree.

8. Pathophysiology .incresed deadspace .hyperventilation .hypoxemia due to : .V/Q mismatch .pulmonary shunt Reduced cardiac output

9. Risk Factors Hypercoagulability Malignancy Nonmalignant thrombophilia Pregnancy Postpartum status (<4wk) Estrogen/ OCP�s Genetic mutations (Factor V Leiden, Protein C & S deficiency, Factor VIII, Prothrombin mutations, anti-thrombin III deficiency) Venous Statis Bedrest > 24 hr Recent cast or external fixator Long-distance travel or prolong automobile travel Obesity Vessel Injury Recent surgery requiring endotracheal intubation Recent trauma (especially the lower extremities and pelvis) 9 Cancers of primarily adenocarcinoma and CNS tumors most often cause thrombosis. We need to make special mention about patients with a prior history of DVT or PE. Studies have revealed these patients have between a 5 to 30 times increased risk of a new DVT in response to a triggering event compared to those who have not had prior episodes. Cancers of primarily adenocarcinoma and CNS tumors most often cause thrombosis. We need to make special mention about patients with a prior history of DVT or PE. Studies have revealed these patients have between a 5 to 30 times increased risk of a new DVT in response to a triggering event compared to those who have not had prior episodes.

10. Clinical Presentation The Classic Triad: (Hemoptysis, Dyspnea, Pleuritic Pain) Not very common! Occurs in less than 20% of patients with documented PE Three Clinical Presentations Pulmonary Infarction Submassive Embolism Massive Embolism : sys pressure< 90 or fall in BP>40 10 All the above symptoms are a manifestation of cardiopulmonary stress caused by the clot in the lung. These produce symptoms perceived by the patient and the signs observed by you! There are three common clinical presentations that you should be aware of: 1. Patient�s with pulmonary infarction may have pleuritic chest pain and can be hard to distinguish between that patient with infection pneumonitis 2. Submassive embolism are the hardest of all. By definition, they have an angiographically defined blockage of flow to an area served by less than two lobar arteries. These patients have acute or unexplained dyspnea with exertion or at rest. So, they can be easily confused with infection, asthma, CHF and the like. 3. Finally, Massive PE, or a clot which obstructs two lobar arteries, so-called �Saddle Embolus�. These patients have acute cor pulmonaly often with syncope. You might think there having an MI or look septic! All the above symptoms are a manifestation of cardiopulmonary stress caused by the clot in the lung. These produce symptoms perceived by the patient and the signs observed by you! There are three common clinical presentations that you should be aware of: 1. Patient�s with pulmonary infarction may have pleuritic chest pain and can be hard to distinguish between that patient with infection pneumonitis 2. Submassive embolism are the hardest of all. By definition, they have an angiographically defined blockage of flow to an area served by less than two lobar arteries. These patients have acute or unexplained dyspnea with exertion or at rest. So, they can be easily confused with infection, asthma, CHF and the like. 3. Finally, Massive PE, or a clot which obstructs two lobar arteries, so-called �Saddle Embolus�. These patients have acute cor pulmonaly often with syncope. You might think there having an MI or look septic!

11. Mythology of PE Myth �Patients with pulmonary embolism are short of breath and have chest pain!� Reality: You can forget about making the diagnosis on clinical grounds, but wait�don�t plan on completely ruling it out either! 11 While it�s true the most common symptom is shortness of breath, even patients with circulatory collapse may have no dyspnea, tachypnea, or pleuritic pain! In fact, A normal paO2 > 80 is more prevalent in patients with pulmonary infarction syndrome. As a simple rule, if you have a patient in your department and you don�t have a good reason to explain there dyspnea, it�s a good idea to consider PE! While it�s true the most common symptom is shortness of breath, even patients with circulatory collapse may have no dyspnea, tachypnea, or pleuritic pain! In fact, A normal paO2 > 80 is more prevalent in patients with pulmonary infarction syndrome. As a simple rule, if you have a patient in your department and you don�t have a good reason to explain there dyspnea, it�s a good idea to consider PE!

12. Clinical Features Symptoms in Patients with Angio Proven PTE Symptom Percent Dyspnea 84 Chest Pain, pleuritic 74 Anxiety 59 Cough 53 Hemoptysis 30 Sweating 27 Chest Pain, nonpleuritic 14 Syncope 13 12 These are the common symptoms that are associated with PE As we mentioned in the previous slide, dyspnea and chest pain are not always present. The explanation is that with a small V/Q mismatch, the adaptive physiology of the pulmonary vasculature and bronchi produce intermittent shortness of breath. Because of this, we are easily distracted and looking for a cardiogenic cause of the dyspnea. What about pleuritic chest pain, still not a home run! In fact, up to 25% of patients ultimately diagnosed with a PE, never had any chest pain! This is what makes the diagnosis so difficult! These are the common symptoms that are associated with PE As we mentioned in the previous slide, dyspnea and chest pain are not always present. The explanation is that with a small V/Q mismatch, the adaptive physiology of the pulmonary vasculature and bronchi produce intermittent shortness of breath. Because of this, we are easily distracted and looking for a cardiogenic cause of the dyspnea. What about pleuritic chest pain, still not a home run! In fact, up to 25% of patients ultimately diagnosed with a PE, never had any chest pain! This is what makes the diagnosis so difficult!

13. Clinical Features Signs with Angiographically Proven PE Sign Percent Tachypnea > 20/min 92 Rales 58 Accentuated S2 53 Tachycardia >100/min 44 Fever > 37.8 43 Diaphoresis 36 S3 or S4 gallop 34 Thrombophebitis 32 Lower extremity edema 24 13 Lets look a t a couple of these: Tachycardia! Myth #2 We are all taught this is a key component of the diagnosis. Right? In fact, actually not having tachycardia is more commonly seen in patients who are found to have a PE! What about fever? If a patient has a fever, it must not be a PE, right? Not true. Although not common, Among patients with PE and no other source of fever, fever was present in one study in 43 of 311 patients (14%). Lets look a t a couple of these: Tachycardia! Myth #2 We are all taught this is a key component of the diagnosis. Right? In fact, actually not having tachycardia is more commonly seen in patients who are found to have a PE! What about fever?

14. Who do we work up? - Pretest Probability Definition: �The probability of the target disorder (PE) before a diagnostic test result is known�. Used to decide how to proceed with diagnostic testing and final disposition 14 For example This could represent the likelihood that a specific patient , say a middle-aged man, with a specific past history, say hypertension and tobacco smoking who presents with a specific symptom complex: Chest pain, Dsypnea, or Diaphoresis has a specific diagnosis. Final Statement: Because PE can present with or with any of the �classic signs and symptoms� and even the risk factors which contribute to PE are varied in frequency, we are left with a intuition at best! For example This could represent the likelihood that a specific patient , say a middle-aged man, with a specific past history, say hypertension and tobacco smoking who presents with a specific symptom complex: Chest pain, Dsypnea, or Diaphoresis has a specific diagnosis. Final Statement: Because PE can present with or with any of the �classic signs and symptoms� and even the risk factors which contribute to PE are varied in frequency, we are left with a intuition at best!

15. Well�s Scoring

16. Prognostic factors Dysfunction of right ventricle Rise of brain natriuretic peptide>90pg/ml Or N-terminal pro-BNP Simultaneous DVT Thrombus in right ventricle Rise of troponin Hyponatremia

17. Diagnostic Test Imaging Studies CXR V/Q Scans Spiral Chest CT Pulmonary Angiography Echocardiograpy Laboratory Analysis CBC, ESR, Hgb/Hct, D-Dimer ABG�s Ancillary Testing EKG Pulse Oximetry 17 As you can see there are a variety of test that we use to arrive at a diagnosis. Some better than others! So, lets talk about these individually. As you can see there are a variety of test that we use to arrive at a diagnosis. Some better than others! So, lets talk about these individually.

18. 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 18 Granted that most are abnormal, but certainly not diagnostic. It is true that in the original PIOPED study it was recommended but the main value is to exclude diagnoses the mimic PE and to aid in the interpretation of the V/Q scanGranted that most are abnormal, but certainly not diagnostic. It is true that in the original PIOPED study it was recommended but the main value is to exclude diagnoses the mimic PE and to aid in the interpretation of the V/Q scan

19. Diagnostic Testing  - CXR�s Chest radiograph findings in patient with pulmonary embolism Result Percent Cardiomegaly 27% Normal study 24% Atelectasis 23% Elevated Hemidiaphragm 20% Pulmonary Artery Enlargement 19% Pleural Effusion 18% Parenchymal Pulmonary Infiltrate 17% 19 Cardiomegaly was the most frequent finding in those with PE of In-patients Out-patients, it seemed to be atelectasis in the above study. Cardiomegaly was the most frequent finding in those with PE of In-patients Out-patients, it seemed to be atelectasis in the above study.

20. Chest X-ray Eponyms of PE Westermark'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. 20

21. Radiographic Eponyms  - Hampton�s Hump, Westermark�s Sign 21 Here we see the dilated vessels and oligemia of westermark�s sign And below Hampton�s HumpHere we see the dilated vessels and oligemia of westermark�s sign And below Hampton�s Hump

22. Diagnostic Testing  � EKG�s EKG Most Common Findings: Tachycardia or nonspecific ST/T-wave changes Acute cor pulmonale or right strain patterns Tall peaked P-waves in lead II (P pulmonale) Right axis deviation RBBB S1-Q3-T3 (occurs in only 20% of PE patients) 22 A brief mention about the classic S1-Q3-T3, its appearance on the EKG may suggest PE, but study after study has shown it has no predictive value what so ever! But you got to know it because question writers for the boards love it!A brief mention about the classic S1-Q3-T3, its appearance on the EKG may suggest PE, but study after study has shown it has no predictive value what so ever! But you got to know it because question writers for the boards love it!

23. 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. 23 Actually, it is opposite of what you might think!Actually, it is opposite of what you might think!

24. 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. 24 As with most dogma, we are taken back by what we thought was truth. About 15% of patients with proven pulmonary embolism have a pO2 of 85mmHg or higher! In one study, researches drew from there data various combinations of the PaO2 of 80mm Hg or more, the PaCO2 of 35mmHg or higher, and the A-a gradient of 20 mmHg or less. They found that PE could not be excluded in more than 30% of patients with no prior cardiopulmonary disease. Moreover, PE could not be excluded in more than 14% of patients with prior cardiopulmonary disease. Conclusion, Blood gas levels are poor discriminate value to permit the exclusion of PE. As with most dogma, we are taken back by what we thought was truth. About 15% of patients with proven pulmonary embolism have a pO2 of 85mmHg or higher! In one study, researches drew from there data various combinations of the PaO2 of 80mm Hg or more, the PaCO2 of 35mmHg or higher, and the A-a gradient of 20 mmHg or less. They found that PE could not be excluded in more than 30% of patients with no prior cardiopulmonary disease. Moreover, PE could not be excluded in more than 14% of patients with prior cardiopulmonary disease. Conclusion, Blood gas levels are poor discriminate value to permit the exclusion of PE.

25. Diagnostic Testing Echocardiography Consider in every patient with a documented pulmonary embolism EKG maybe helpful in demonstrating right heart strain Early fibrinolysis can reduce mortality 50%! 25 Diagnosing of early right ventricular strain is important because it is a strong predictor of subsequent death Important to recommend echocardiogram with your admitting internist if a pattern of right heart strain is suggested by EKG. Studies have documented that lives are saved with early fibrinolysis is considered in these patients. Diagnosing of early right ventricular strain is important because it is a strong predictor of subsequent death Important to recommend echocardiogram with your admitting internist if a pattern of right heart strain is suggested by EKG. Studies have documented that lives are saved with early fibrinolysis is considered in these patients.

26. Ancillary Test WBC Poor sensitivity and nonspecific Can be as high as 20,000 in some patients Hgb/Hct PTE does not alter count but if extreme, consider polycythemia, a known risk factor ESR Don�t get one, terrible test in regard to any predictive value 26

27. D-dimer Test Fibrin 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 week Malignancy Surgery within 1 week Advanced age > 80 years Sepsis Hemmorrhage CVA AMI Collagen Vascular Diseases Hepatic Impairment 27 Well, what is it? Basically, the assay is enzyme-linked monoclonal antibody test used to identify the protein, D-Dimer. D-Dimer itself is a unique degradation product that is produced by a plasmin mediated breakdown of cross-linked fibrin Good test with respect to its negative predictive value. The drawbacks are some of the false positives that we commonly see in the ER. Well, what is it? Basically, the assay is enzyme-linked monoclonal antibody test used to identify the protein, D-Dimer. D-Dimer itself is a unique degradation product that is produced by a plasmin mediated breakdown of cross-linked fibrin Good test with respect to its negative predictive value. The drawbacks are some of the false positives that we commonly see in the ER.

28. Diagnostic Testing D-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 28 Two types, Qualitative RBC agglutination assay, low sensitivity and specificity and not good enough to comfortably rule out PE. Quantitative, which measure the accurately the amount using a spectrophotometer. Our lab uses the 2nd generation VIDAS d-dimer with a negative predictive value of 99.3%! Two types, Qualitative RBC agglutination assay, low sensitivity and specificity and not good enough to comfortably rule out PE. Quantitative, which measure the accurately the amount using a spectrophotometer. Our lab uses the 2nd generation VIDAS d-dimer with a negative predictive value of 99.3%!

29. 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 50mrad vs 800mrad (with spiral CT) 29

31. V/Q Scan Technique Interpretation Normal Low probability/�nondiagnostic� (most common) High Probability Simplified approached to the interpretation of results: High probability ? Treat for PE Normal Scan ? If low pre-test, your done Everything else ? Purse another study (CT, Angio) 31 Essentially, a patient is injected with a radioisotope that travels through the pulmonary microcirculation and are detected by a gamma camera over the patient A normal Perfusion study will have evenly distributed blood flow. Then a patient inhales a radioactive gas and it is viewed as it washes over the bronchopulmonary tree. A mismatch, areas of blocked perfusion and normal ventilation is interpreted by the radiologist and given reading as normal (never), high probability, or non-diagnostic/low-probability The reason the low probability or non diagnostic scan category is so suspect is because in the PIOPED study this group had terrible inter-reader reliability. So, just beware. Essentially, a patient is injected with a radioisotope that travels through the pulmonary microcirculation and are detected by a gamma camera over the patient A normal Perfusion study will have evenly distributed blood flow. Then a patient inhales a radioactive gas and it is viewed as it washes over the bronchopulmonary tree. A mismatch, areas of blocked perfusion and normal ventilation is interpreted by the radiologist and given reading as normal (never), high probability, or non-diagnostic/low-probability The reason the low probability or non diagnostic scan category is so suspect is because in the PIOPED study this group had terrible inter-reader reliability. So, just beware.

32. Spiral (Helical) Chest CT Advantages Noninvasive and Rapid Alternative Diagnosis Disadvantages Costly ($600 - 900/scan) Risk to patients with borderline renal function Hard to detect subsegmental pulmonary emboli 32 The entire lung can be scanned while the patient holds there breath. Advantages: CT most useful benefit is in providing evidence for an alternative diagnosis or excluding it entirely. Disadvantages: The clinical significance for subsegmental PE are not well known, but may be a marker for a larger PE Given that the majority of V/Q studies are non-diagnostic, I prefer the CT as the initial test of choice in place of V/Q scan. The entire lung can be scanned while the patient holds there breath. Advantages: CT most useful benefit is in providing evidence for an alternative diagnosis or excluding it entirely. Disadvantages: The clinical significance for subsegmental PE are not well known, but may be a marker for a larger PE Given that the majority of V/Q studies are non-diagnostic, I prefer the CT as the initial test of choice in place of V/Q scan.

37. Pulmonary Angiography �Gold Standard� Performed in an Interventional Cath Lab Positive result is a �cutoff� of flow or intraluminal filling defect �Court of Last Resort� 37 Right now there is no better test on the horizon of the immediate present to virtually rule out or in PE. Right now there is no better test on the horizon of the immediate present to virtually rule out or in PE.

39. Treatment: Goals: Prevent death from a current embolic event Reduce the likelihood of recurrent embolic events Minimize the long-term morbidity of the event 39 I thought this cartoon kind of summarizes how patients sometimes feel about the medical jargon we throw about and the puzzled look are there face when we try to explain this condition and how to treat it. So what are our goals???I thought this cartoon kind of summarizes how patients sometimes feel about the medical jargon we throw about and the puzzled look are there face when we try to explain this condition and how to treat it. So what are our goals???

40. Treatment Anticoagulants Heparin Provides immediate thrombin inhibition, which prevents thrombus extension Does not dissolve existing clot Will not work in patients with antithrombin III def. In this case use hirudins Few absolute contraindications 40 Heparin is the most frequently used drug in the treatment of PE. Because heparin works by activating antithrombin III, this genetic mutation makes heparin ineffective. Heparin is the most frequently used drug in the treatment of PE. Because heparin works by activating antithrombin III, this genetic mutation makes heparin ineffective.

41. Treatment Anticoagulants Heparin Available as Unfractionated or LMW Heparin FDA approved dosing: Unfractionated: 80 units/kg bolus, 18 units/kg/hr LMWH: 1 mg/kg Q 12 or 1.5mg/kg Q D LMWH (Lovenox) prefered in pregnant patients 41 FDA approved dose for Unfractionated heparin is 80units/kg IV bolus, then 18 units/kg/hr infusion to maintain the INR at 2.5-3 Lovenox is dosed at 1mg/kg every 12 hours or 1.5 mg/kg per day. LMWH in pregnancy only preferred for convenience sake. FDA approved dose for Unfractionated heparin is 80units/kg IV bolus, then 18 units/kg/hr infusion to maintain the INR at 2.5-3 Lovenox is dosed at 1mg/kg every 12 hours or 1.5 mg/kg per day. LMWH in pregnancy only preferred for convenience sake.

42. Treatment Anticoagulants Warfarin (Coumadin) Interferes with the action of Vit-K dependent factors: II, VII, IX, and X, as well as protein C & S Causes temporary hypercoagulable state in first 5 days of treatment Important a patient is anticoagulated with heparin before initiating warfarin therapy Target INR is 2.5 � 3.0 42 This is because the anticoagulants protein C and S have short half-lives compared with the procoagulant vitamin K-dependent proteins. So, this gives rise to the clinical importance that heparin must be continued for at least five days after beginning Coumadin The incidence of progressive thrombosis and embolization is 40% when starting warfarin directly, compared to only 8% when beginning after a patient has been anticoagulated with heparin. Treatment is usually for 6 months, but may continue lifelongThis is because the anticoagulants protein C and S have short half-lives compared with the procoagulant vitamin K-dependent proteins. So, this gives rise to the clinical importance that heparin must be continued for at least five days after beginning Coumadin The incidence of progressive thrombosis and embolization is 40% when starting warfarin directly, compared to only 8% when beginning after a patient has been anticoagulated with heparin. Treatment is usually for 6 months, but may continue lifelong

43. Treatment Fibrinolytic Therapy (Alteplase) Indications: Documented PE with: Persistent hypotension Syncope with persistent hemodynamic compromise Significant hypoxemia +/- patient with acute right heart strain Approved alteplase regimen is 100mg as a continuous IV infusion. 43 For critically ill patients, a very rapid infusion of 100mg over 10 minutes is preferred. Alternative is Retavase, you can give it as two IV doses of 10 units, each over two minutes. For critically ill patients, a very rapid infusion of 100mg over 10 minutes is preferred. Alternative is Retavase, you can give it as two IV doses of 10 units, each over two minutes.

44. Contraindication to fibrinolytic therapy Absolute: History of hemorrhagic stroke Active intracranial neoplasm Recent <2 month intracranial surgery Active or recent internal bleeding in prior 6 month Relative: Bleeding diathesis Uncontrolled severe hypertension> 200/110 Nonhemorrhagic stroke Surgery whithin previous 10 days Thrombocytopenia< 100000

45. Treatment Embolectomy Prefininolytic therapy this was only therapy for massive PE Carries a 40% operative mortality Alternative is Transvenous Catheter Embolectomy 45 This is a procedure where a suction tip catheter is placed in contact with the thrombus under fluoroscopy and sucked out while catheter is withdrawnThis is a procedure where a suction tip catheter is placed in contact with the thrombus under fluoroscopy and sucked out while catheter is withdrawn

46. A Simplified Algorithm Pre-test probability D-dimer (VIDAS-DD) CT angiography 46 The simplest algorithm says you can safely rule out PE in a low pre-test patient with a negative D-dimer I believe our institution and my personal practice is similar to the Mayo Clinic Group who uses a combination of pre-test probability, D-dimers, and CT angio, and limited V/Q to arrive at a disposition. The simplest algorithm says you can safely rule out PE in a low pre-test patient with a negative D-dimer I believe our institution and my personal practice is similar to the Mayo Clinic Group who uses a combination of pre-test probability, D-dimers, and CT angio, and limited V/Q to arrive at a disposition.

47. Special Circumstances Morbid Obesity Pregnancy V/Q has considerable less radiation 50mrad vs. 800 mrad Almost all will have positive D-Dimer Heparin safe in pregnancy Witnessed Cardiac Arrest Standard ACLS, if known PE, the lytics. 47 These patients are difficult if not impossible to image. D-dimer may be useful if < 500 and you can support an alternative diagnosis. These patients are difficult if not impossible to image. D-dimer may be useful if < 500 and you can support an alternative diagnosis.

48. Conclusion Summary 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), then disposition) 48

49. The End! 49

50. 1. Which of the following is not a part of virchows triad? Hypercoagulability Stasis to flow Vessel injury History of previous DVT 50

51. Which of the following is the propper treatment of fat emboli? Platelets High dose steroids Heparin cryoprecipitate 51

52. The Classic Triad of patients presenting to the ED with PE includes all of the following except: Hemoptysis Dyspnea + Homans� sign Pleuritic Pain 52

53. What is the most common symptom in a patient with Angio Proven PTE? Dyspnea Chest Pain, pleuritic Anxiety Cough 53

54. What is the most common ecg finding in patients with PE? Right axis deviation RBBB S1-Q3-T3 Tall peaked T-waves in lead II (P pulmonale) Sinus tachycardia 54

55. Answers D B C A E 55