Emergency Medicine Pulmonary Embolism Case File

Emergency Medicine Pulmonary Embolism Case File

Eugene C. Toy, MD, Barry C. Simon, MD, Terrence H. Liu, MD, MHP, Katrin Y. Takenaka, MD, Adam J. Rosh, MD, MS

Case 16

A 34-year-old man presents to the emergency department (ED) complaining of shortness of breath and chest pain that he describes as right sided and increased with deep breathing. He states it started suddenly when he woke up and was worse with activity. He denies fever, chills, nausea, vomiting, or cough. He has a recent history of multiple gunshot wounds resulting in ongoing pain in his upper back and T-10 paraplegia. One week ago, he was discharged from the hospital to a rehabilitation facility. He is currently taking acetaminophen/hydrocodone and ibuprofen for his pain, which has increased with his physical therapy and occupational therapy. He is also taking hydrochlorothiazide and lisinopril for hypertension and fluoxetine for depression. He recently quit smoking tobacco since he was hospitalized and denies any alcohol or illicit drug use. On physical examination, he is an otherwise fit young man who appears slightly short of breath and uncomfortable. His heart rate is 101 beats per minute, his blood pressure is 110/78 mm Hg, and his respiratory rate is 26 breaths per minute. His pulse oximetry is 96% on 2 L of O2 by nasal canula. His lungs are clear to auscultation. There is mild swelling of his left calf. He has no sensation in his lower extremities. Laboratory studies reveal a white blood cell count (WBC) of 10,000/mm³. Hemoglobin, hematocrit, electrolytes, and renal function are all within normal limits. A 12-lead electrocardiogram (ECG) reveals a sinus rhythm at a rate of 103 beats per minute. His chest radiograph reveals minimal bibasilar atelectasis but no evidence of infiltrates or effusions.

⯈ What is the most likely diagnosis?

⯈ What is your next diagnostic step?

ANSWER TO CASE 16:

Pulmonary Embolism

Summary: A 34-year-old man with hypertension, depression, and recent gunshot wounds resulting in T-10 paraplegia presents with dyspnea, pleuritic and right-sided chest pain, tachypnea, tachycardia, left calf swelling, and bibasilar atelectasis on chest radiography.

• Most likely diagnosis: Pulmonary embolism (PE) secondary to deep venous thrombosis (DVT) in the left lower extremity.
• Screening and confirmatory studies: For evaluation of PE, D-dimer level, venous duplex ultrasonography, ventilation-perfusion scan (V/Q scan), pulmonary CT angiography, and catheter pulmonary angiography are available and may be applied on a selective basis.

ANALYSIS

Objectives

1. Learn the clinical presentations of PE.
2. Learn to formulate reasonable diagnostic strategy for the diagnosis of pulmonary embolism in the emergency department setting.
3. Learn the sensitivity, specificity, and limitations of the D-dimer test and the contrast-enhanced helical computed tomography angiogram for the diagnosis of DVT and PE.

Considerations

This 34-year-old patient who has been immobilized has a primary risk factor for venous thromboembolism. The presentation of acute dyspnea, chest pain, borderline tachycardia, and unilateral lower extremity swelling in the absence of identifiable alternative cardiopulmonary disease place him in the high-risk category for a pulmonary embolism. An ECG in patients with suspected PE is generally helpful for identifying other etiologies of his symptoms such as ischemic heart disease, pericarditis, and dysrhythmias. In some instances, the ECG may reveal right-heart strain patterns that are more specific for the diagnosis of PE. Although nonspecific, sinus tachycardia is still the most frequent presenting ECG finding among patients with PE. Even 25% of patients with identified PE may have a normal ECG. The relatively normal chest radiograph is valuable in eliminating alternative diagnoses, such as pneumonia, pneumothorax, and congestive heart failure. An arterial blood gas can be used to assess patients with shortness of breath, but it is non-specific in the diagnosis of PE. Taking into consideration the clinical, radiographic, and ECG data, a presumptive diagnosis of PE can be made. The next steps in management include maintenance of cardiopulmonary stability, consideration of empiric anticoagulation therapy, and confirmation of the diagnosis.

Approach To:

DVT and PE

DEFINITIONS

DEEP VENOUS THROMBOSIS: Formation of clot (thrombus) in a deep vein (a vein that accompanies an artery). Eighty to ninety percent of diagnosed PEs arise from a DVT of the lower extremity. However, thrombi of deep veins in the calf (tibial veins) are difficult to detect, but also much less likely to embolize than more proximal thrombi.

PULMONARY EMBOLISM: Blockages of the pulmonary arteries, most often caused by blood clots originating from deep veins in the legs or pelvis. In rare circumstances, air bubbles, fat droplets, amniotic fluid, clumps of parasites, or tumor cells may also cause a PE. Risk factors for thrombosis are related to Virchow triad of hypercoagulability, venous stasis, and venous injury.

D-DIMER ASSAY: Fibrin D-dimer is released into the circulation following degradation of cross linked fibrin by plasmin. Multiple commercial assays are available that use a monoclonal antibody to detect the D-dimer fragment. The two most commonly used assays are the whole blood immunoagglutination test (less accurate) and the quantitative plasma ELISA assay (more accurate). Elevated levels may indicate the presence of concurrent thrombus formation and degradation. Other conditions in which D-dimer elevation occurs include sepsis, recent myocardial infarction or stroke (<10 days), recent surgery or trauma, disseminated intravascular coagulation, collagen vascular disease, metastatic cancer, pregnancy, hospitalized patients and liver disease. The D-dimer may be falsely negative if clot formation is greater than 72 hours before the blood is assayed. Conversely, it may be falsely positive since levels may remain elevated for as long as 2 years. In pregnancy, the upper limits of normal are increased with each trimester, but a true normal D-dimer should never be greater than 1000 μg/L.

VENOUS DUPLEX ULTRASONOGRAPHY: Ultrasound imaging modality combining direct visualization of veins with Doppler flow signal to assess luminal patency and compressibility of the deep venous system in the extremities and the presence of thrombosis. This imaging modality is most accurate for assessment of the iliac, femoral, and popliteal veins.

PERFUSION AND VENTILATION (V/Q) SCAN: Radioisotope used to identify ventilation perfusion mismatches. Results are categorized into probabilityranked groups after taking into account of coexisting pulmonary pathology and the patient’s overall clinical picture. Radiologists interpret V/Q scans as normal, low, intermediate or high probability for V/Q mismatch or PE in the right clinical setting. Unfortunately, many patients with known PE have nondiagnostic V/Q scans, and these low to intermediate probability scans have significant disagreement among interpreters. Current literature indicates its benefits primarily in renal failure when contrast may precipitate renal failure. V/Q scans may also be the test of choice for pregnant patients. It is reported that multidetector CT (MDCT) scanning has higher radiation exposure for the mother but lower fetal radiation exposure, whereas V/Q scan has lower maternal and higher fetal radiation exposure. Remy-Jardin recommends perfusion scintigraphy (Q) without ventilations scintigraphy (V), which significantly decreases fetal radiation exposure.

COMPUTED TOMOGRAPHY PULMONARY ANGIOGRAPHY (CTPA): Magnified CT imaging of the pulmonary vasculature obtained during the arterial phases of venous contrast injection. While highly specific for PE, the reported sensitivity is variable and ranges from 50% to 90%. The diagnostic sensitivity is higher for centrally located PE but reduced for subsegmental clots. The Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) study suggests that CTPA identifies more PE than V/Q scanning, but these may be false-positives or clots that do not require anticoagulation. The diagnostic accuracy is also related to observer expertise. The initiation of multidetector CT scanning has greatly improved imaging of central, segmental, and subsegmental arteries. An advantage of this modality is its ability to detect alternative diagnoses. Pulmonary MDCT angiography has a reported sensitivity of 83% and a specificity of 96% in PIOPED II.

PULMONARY ANGIOGRAPHY: Imaging involving intravascular contrast injection and fluoroscopy to determine patency of the pulmonary arterial vasculature. Although once considered the gold standard for diagnosing PE, this test has largely been replaced by pulmonary CT angiography (CTA). Baile et al showed that these two tests had no difference in the detection of subsegmental sized PE. They concluded that pulmonary CTA and pulmonary angiography are comparable for detecting PE. Pulmonary angiography is invasive and is associated with increased morbidity and mortality when compared to CTA.

CLINICAL APPROACH

Deep Venous Thrombosis

Up to 60% of patients with untreated proximal DVT will develop PE; consequently, accurate diagnosis of this condition is critical for emergency physicians. Unfortunately, the clinical features of DVT are frequently nonspecific, and may include pain, tenderness, swelling, edema, and erythema. The physical examination and thromboembolic risk factors (Table 16–1) are important in assessing the clinical suspicion (ie, pretest probability), and based on the pretest probability, clinical algorithm for the diagnosis of lower extremity DVT may be formulated (Figure 16–1).

Duplex ultrasound is the most common test used to evaluate for the presence of DVT. Its accuracy approaches 98% for proximal DVT detection, when an experienced operator performs the test. ELISA D-dimer can serve as a screening tool for DVT. In practice, a positive ELISA D-dimer is not of any clinical value. However, due to its high sensitivity, a negative ELISA D-dimer suggests the absence of an acute thrombus. In patients with low pretest probability and a negative ELISA D-dimer, the diagnosis of DVT can be ruled out. Venography is the traditional gold standard for DVT. However, due to its invasiveness, risk of reaction to contrast dye, and the advent of newer technologies that are just as accurate, venography is rarely used in clinical practice.

All patients diagnosed with a DVT at or above the popliteal level should be treated with anticoagulation. Treatment goals are directed toward the prevention

Figure 16–1. Algorithm for diagnosis of suspected lower extremity DVT.

of thrombus propagation and embolization. In patients with extensive DVT that involves the iliac and femoral veins, the use of thrombolytic therapy should be considered to help minimize the postphlebitic sequelae. For most patients, acute management consists of anticoagulation with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). When UFH therapy is selected, it is vital to achieve therapeutic levels rapidly. When this is accomplished within 24 hours, the DVT recurrence rate is 4% to 6%, compared to 23% when therapeutic levels are delayed. LMWH can be administered for the treatment of DVT with or without PE. Enoxaparin is a commonly used LMWH (Table 16–2). Patients developing recurrent DVT during optimal anticoagulation therapy should undergo evaluation for hypercoagulability conditions and be considered for inferior vena cava (IVC) filter placement (eg, Greenfield filter). IVC filters are also useful for individuals with contraindications to anticoagulation. However, these filters present their own risks for developing thrombosis and PE and have limited effect over time.

Pulmonary Embolism

Few common medical conditions are as difficult to diagnose as PE. The majority of patients have dyspnea and chest pain at presentation, whereas cardiovascular collapse is observed in 10% of the patients. Symptoms of PE include sudden onset cough (3%-55%), blood-streaked sputum (3%-40%), sudden onset of dyspnea at rest or with exertion (75%), splinting of ribs with breathing, chest pain (50%-85%), and diaphoresis (25%-40%). Nonspecific signs of PE include tachypnea (50%-60%), tachycardia (25%-70%), rales/crackles (50%), and low-grade fever (7%-50%), the latter of which is suggestive of pulmonary infarction. Tachypnea is the most commonly reported sign in patients diagnosed with PE. Chest pain associated with PE is commonly pleurtitic in nature. The “classic triad” for PE (hemoptysis, dyspnea,

^aWarfarin should always be administered in conjunction with either unfractionated or low molecular weight heparin until

a therapeutic INR level is achieved.

and chest pain) occurs in fewer than 20% of patients in whom PE is diagnosed. PE is occasionally diagnosed in young, active patients presenting to the ED complaining only of pleuritic chest pain. Such patients are often dismissed inappropriately with inadequate workups and nonspecific diagnoses such as musculoskeletal chest pain or pleurisy. Spontaneous onset of chest wall tenderness without a history of trauma is worrisome, because this may be the only physical finding of PE. In a recent study by Courtney et al, non–cancer-related throbophilia, pleuritic chest pain and family history of VTE increased the probablility of PE or DVT. Unusual clinical presentations of PE also include seizure, syncope, abdominal pain, high fever, productive cough, adult-onset asthma, new-onset supraventricular arrhythmias, or hiccups.

Diagnosis

The diagnosis of PE remains a difficult task despite the multitude of resources. Routine tests obtained in the ED, such as radiographs, ABGs, and ECG provide limited and nonspecific information. In an effort to make the correct diagnosis, EPs must calculate a pretest probability for PE. There are multiple scoring systems available that attempt to classify patients into low, intermediate, and high-risk categories. A commonly used scoring system is the Wells criteria (Table 16–3). Based on findings from the PIOPED study, clinicians correctly excluded pulmonary embolism 91% of the time in low-clinical-probability patients; however, in the intermediate- and high-probability patients, clinicians correctly diagnosed PE only 64% to 68% of the time. Because clinical variables alone lack power to permit treatment decisions, patients with intermediate to high probability must undergo further testing until the diagnosis is proven, ruled out, or an alternative diagnosis is identified.

The Pulmonary Embolism Rule-Out Criteria (PERC) is another commonly used clinical decision rule (Table 16–4). This rule only applies to those who are low risk for PE. If eight of the clinical criteria are met, then there is less than a 2% risk that the patient has a PE and no further work-up is needed.

Data from Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patient’s probability

of pulmonary embolism: increasing the model’s utility with the simpliRED D-dimer. Thromb Haemost. 2000;83:416-420.

The initial chest radiograph (CXR) in a patient with PE is abnormal in 76% to 90% of patients. However, there is no finding on chest radiograph that is diagnostic of PE. Rarely, the classic Westermark sign (peripheral lung vasoconstriction) and Hampton hump (pleural wedge-shaped density associated with pulmonary infarction) are seen. Serial CXRs obtained in a patient with PE are frequently associated with progression suggestive of atelectasis, pleural effusion, and elevated hemidiaphragm. After 2 to 3 days, the CXR in one-third of patients with PE demonstrates focal infiltrates mimicking pneumonia. Because of the variability in these findings, chest radiography is of limited use in diagnosing PE.

Interpretation of nuclear scintigraphic ventilation-perfusion scanning (V/Q scan) may group patients into four result types: normal, low probability, indeterminant, and high probability. Similar to the diagnosis of DVT, the clinical suspicion determines the pretest probability and the accuracy of V/Q scans. Therefore, the subsequent management following V/Q scans should be formulated on the basis of clinical impression and V/Q scan interpretations. One study reported that V/Q scan combined with chest radiography had the same diagnostic accuracy as pulmonary CTA and V/Q scanning.

High-resolution CT angiography has become the standard initial diagnostic test for the evaluation of high risk patients for PE. Additionally, MDCTA has largely replaced single-detector CT scanners. MDCTA, according to PIOPED II, has a sensitivity of 83% and a specificity of 96% for diagnosing PE. A negative pulmonary MDCTA can safely exclude a PE. It has a positive predictive value of 86% and a negative predictive value of 95%. Due to limitations of PIOPED II, these results may not apply to patients with renal failure, pregnant women, and critically ill patients.

The addition of indirect CT venography (CTV) was also investigated in PIOPED II. Although they reported a statistically insignificant increase in sensitivity (83%- 90%), specificity was not changed. CTV increases the radiation exposure and has the equivalent diagnostic results as lower-extremity sonography. It should be used with caution in younger patients who have the greatest long-term risk of radiation exposure. It has the advantage of having the patient only undergo one test and getting information on the pulmonary and venous system. Remy-Jardin reported that the greatest benefit from the addition of CTV to CTA has been shown in sicker patients, in centers with less experience, and with older equipment.

In high pre-test clinical probability patients who have a negative MDCTA test for PE, further testing is recommended. These patients represent a discordant group— high risk but with a negative test. Options include repeat pulmonary MDCTA if there were technical problems with the first test, pulmonary angiography, V/Q scan, or lower extremity venous sonography.

Pulse oximetry and ABG measurements are insensitive in identifying PE and should never be used to direct diagnostic workup. Despite the common practice of obtaining ABGs in the workup of PE, multiple studies demonstrate that a normal PaO2, normal PCO2, and normal A-a oxygen gradient does not exclude the diagnosis of PE.

Many recent investigations have focused on the use of the D-dimer assay for PE and DVT diagnosis. D-dimer is a cleavage product created by the degradation of cross-linked fibrin strands by the fibrinolytic system. The power of the D-dimer test is in its negative predictive value rather than its positive predictive value, provided a highly sensitive assay is chosen. A normal D-dimer value is helpful for the exclusion of PE in patients with low pretest probability; however, because intravascular thrombosis may occur in conditions other than PE and DVT, the specificity of elevated D-dimer is limited. It is important to bear in mind that a combination of clinical history, physical examination findings, laboratory studies, and diagnostic investigations are frequently needed for the evaluation of high-risk patients. In high-risk individuals, negative D-dimer assay alone cannot effectively rule out PE, therefore imaging studies such as venous duplex ultrasonography, V/Q scan, CTPA, or pulmonary angiogram are needed to exclude the diagnosis.

Clinical Decision Making

Ultimately, it is the clinician’s burden to combine the imaging and laboratory test results with clinical impression to determine whether treatment for DVT/PE is indicated. Figure 16–2 is a clinical pathway utilizing the Wells criteria for pretest probability to evaluate for PE. The treatment for pulmonary embolism is generally intravenous heparin therapy in conjunction with initiation of warfarin therapy (see Table 16–2). Thrombolytic therapy has been advocated for those individuals with a massive PE, such as those with hypotension for whom mortality is as high as 20% to 30%. There are no conclusive studies that prove a survival advantage for thrombolytic therapy in PE.

Figure 16–2. Diagnostic strategy for patients with suspected PE. (Data from Wells PS, Ginsberg

JS, Anderson DR, et al. Use of a clinical model for safe management of patients with suspected

pulmonary embolism. Ann Intern Med. 1998;129(12):997-1005.)

COMPREHENSION QUESTIONS

16.1 Which of the following statements regarding DVT is most accurate?

A. A patient with thrombosis of the superficial femoral vein is never at risk for PE.

B. Venography is the definitive test for the diagnosis of DVT.

C. Thrombosis of the vena cava, subclavian veins, and right atrium are frequent sources of PE.

D. Venous duplex ultrasonography is most useful in diagnosing DVT in the pelvic veins.

E. Cancer successfully treated 5 years ago is associated with a higher risk for DVT.

16.2 A 52-year-old healthy man presents with a 3-day history of a pleuritic chest pain and SOB. He has normal vital signs and physical examination. Which test is most useful in ruling out this patient for pulmonary emboli?

A. Electrocardiogram (ECG)

B. Chest x-ray

C. Arterial blood gas (ABG)

D. D-dimer level

E. Oxygen saturation

16.3 Which of the following patients with shortness of breath has the lowest clinical probability for PE?

A. A 67-year-old man who underwent bilateral total knee replacements 2 weeks ago

B. A 38-year-old man who underwent an uncomplicated open appendectomy 3 weeks ago

C. A 35-year-old woman with a history of ovarian cancer

D. A 35-year-old man with a history of a DVT 15 years ago, which occurred after an accident

E. A 26-year-old woman who had an uncomplicated vaginal delivery 10 days ago

16.4 A 57-year-old man presents to the ED complaining of shortness of breath. The onset was sudden, and is associated with pleuritic chest pain. He was recently released from the hospital after being diagnosed with lymphoma. He had an indwelling catheter placed in his left subclavian vein the day before for chemotherapy administration. He was previously healthy without significant medical history. His vital signs are heart rate of 105 beats per minute, blood pressure 126/86 mm Hg, respiratory rate of 28 breaths per minute, O2 saturation 100% on room air. The breath sounds are clear bilaterally. His heart sounds are normal without an S3 or S4 gallop. His left arm is mildly edematous, but otherwise painless, with a normal pulse examination. There is no swelling of his lower extremities and he has no pain with palpation of his calves. His catheter incision site is clean and intact. Which of the following studies is inappropriate for this patient?

A. Chest x-ray

B. ECG

C. Contrast CT scan of the chest

D. D-dimer assay

E. Duplex ultrasonography of the deep veins of the upper and lower extremities

ANSWERS

16.1 B. Venography is the gold standard for diagnosing thromboses of the deep veins of the extremities and is useful when duplex studies are inconclusive in high-risk, high-probability patients. Duplex ultrasonography combines direct visualization of the vein with Doppler flow signals. Part of the study relies on the examiner’s ability to visualize compression of the veins to rule out an occluding thrombus. Because intra-abdominal and pelvic veins are difficult to compress, their evaluation by this method is limited. Most clinically significant PE derives from the large veins of the lower extremity, especially the iliofemoral veins that can embolize large clots to the pulmonary vasculature with disastrous hemodynamic consequences. Infrequent sources of PE can be central veins of the upper extremity, the vena cava, or even the right atrium. Despite its name, the superficial femoral vein is considered a deep vein (it accompanies the superficial femoral artery), and can be the source of clinically significant thromboemboli. Active cancer, rather than a history of treated cancer (>5 years) is associated with a higher risk of DVT.

16.2 D. ECG findings are often normal or nonspecific in patients with PE. ST- segment and T-wave abnormalities are the most common, but occasionally signs of right-heart stain may be noted, including peaked P waves in lead II (P pulmonale), right-bundle-branch block, supraventricular arrhythmias, and right-axis deviation. The classic ECG findings of PE are S wave in lead I, Q wave in lead III, and inverted T wave in lead III (S1Q3T3); however, this is rarely seen. ECGs may help to diagnose other etiologies of chest pain and shortness of breath such as pericarditis or tachydysrhythmias. Chest radiographs are also usually normal. In severe PE, dilation of proximal pulmonary vessels with collapse of distal vasculature is noted (Westermark sign). Twenty-four to seventy-two hours after a PE, atelectasis and a focal infiltrate may be seen as a consequence of loss of surfactant. Pleural effusions may be noted, and, rarely, a triangular or rounded pleural-based infiltrate with its apex pointed to the hilum (Hampton hump) may be seen in the case of an infarction. ABG findings are often confusing, and abnormalities are usually a result of underlying pathology such as chronic obstructive pulmonary disease (COPD) or pneumonia. A low PO2 in an otherwise healthy patient at risk for DVT/PE is more useful. O2 saturation is rarely depressed and not very useful in the workup of PE. High sensitivity D-dimer levels are most useful for their negative predictive value in helping to rule out PE in low to moderate pretest-probability patients. It is a very sensitive, but nonspecific test. A normal high sensitivity D-dimer level in a low to moderate pretest probability patient makes PE unlikely and further diagnostic workup is not indicated.

16.3 B. Malignancy, acquired or inherited hypercoagulable states, previous DVT or PE, immobility, and pregnancy are all risk factors for DVT and PE. Although surgery is a known risk factor, the length of the operation and time of postoperative immobility are factors that contribute to thrombosis. The patient who underwent a noncomplicated appendectomy is at minimal risk for a DVT. Patient with the bilateral knee replacement would have very limited mobility for a long period time putting him at risk for DVT and PE. Patient with ovarian cancer is at risk because of her malignancy. A patient with a previous DVT certainly has a greater lifetime risk for recurrence of a DVT. Patient had a normal vaginal delivery 10 days previously would have a higher risk of DVT than the general population.

16.4 D. This patient may very well have a PE, but other sources of his chest pain and shortness of breath must also be considered. An ECG will aid in the diagnosis of cardiac etiologies including heart attacks or arrhythmias. A chest x-ray will show other possible pulmonary processes, including pneumonia or a pneumothorax from the central line placement (as well as confirm the position of the line). Duplex ultrasonography will help examine the venous system for thromboses and possible sources of PE, including the deep veins of the upper extremity, because this patient now has an indwelling catheter that can be a source of thrombus formation. A D-dimer assay is not useful in this patient because he is a high-probability patient and this test should only be ordered in low-probability patients. CTA would be an appropriate test to order in this patient as it can diagnose a PE as well as other etiologies of his symptoms. Also, pulmonary angiography is not yet indicated in this patient until further diagnostic workup leads one to suspect a PE as the source of his symptoms with an otherwise negative workup. Pulmonary angiography is invasive, costly, time consuming, and not without its own complications, and should therefore be used judiciously.

CLINICAL PEARLS

⯈ High clinical suspicion is the most important factor in determining the workup of PE, as its presentation is often elusive.

⯈ High-sensitive D-dimer study is useful for its negative predictive value in excluding DVT and PE.

⯈ V/Q scan is useful in risk-stratifying renal failure and possibly the pregnant patient with suspected PE.

⯈ MDCTA has become the initial test of choice for patients with a high pre-test probability for PE and no contraindications.

⯈ Eighty percent of PEs develop from DVTs involving the iliac, femoral, or popliteal veins.

References

Anderson DR, Kahn SR, Rodger MA, et al. Computed tomographic pulmonary angiography vs. ventilation perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298(23):2743-2753. 

Baile EM, King GG, Muller NL, et al. Spiral computed tomography is comparable to angiography for the diagnosis of pulmonary embolism. Am J Respir Crit Care Med. 2000;161(3 Pt 1):1010-5. 

Courtney M, Kline J, et al. Clinical features from the history and physical examination that predict the presence of absence of pulmonary emobolism in symptomatic emergency department patients: results of a prospective, multi-center study. Ann Emerg Med. 2010; 55 (4):307-315. 

Kline JA, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008;6:772-780. 

Kline, JA, Runyon, MS. Pulmonary embolism and deep vein thrombosis. In: Marx JA, Hockberger RS, Walls RM, eds. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 6th ed. Philadelphia, PA: Mosby Elsevier; 2006. 

Kline, JA. Pulmonary embolism. In: Tintinalli JE, Kelen GD, Stapczynski JS, eds. Emergency Medicine: A Comprehensive Study Guide. 6th ed. New York, NY: McGraw-Hill; 2004. 

Rogers RL, Winters M, Mayo D. Pulmonary embolism: remember that patient you saw last night? Emerg Med Pract. 2004;6(6):1-20. 

Rosen CL, Tracy JA. The diagnosis of lower extremity deep venous thrombosis. Emerg Med Clin North Am. 2001;19:895-912. 

Sadigh G, Kelly A, Cronin P. Challenges, controversies, and hot topics in pulmonary embolism imaging. AJR. 2011:196(3);497-515. 

Sadosty AT, Boie ET, Stead LG. Pulmonary embolism. Emerg Med Clin North Am. 2003;21(2):363-384. 

Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer. Ann Intern Med. 2001;135(2):98-107.

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