Table of Contents

 

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal Of The Literature
5. History And Pathophysiology
6. Prehospital Care
7. Emergency Department Evaluation
   1. History, Physical Examination, And Risk Stratification
8. Diagnostic Studies
   1. Chest X-ray
   2. Electrocardiogram
   3. Arterial Blood Gas Analysis
   4. D-dimer
   5. Computerized Tomographic Pulmonary Angiography
   6. Ventilation/Perfusion Scanning
   7. Bedside Cardiac Echocardiography
   8. Venous Compression Ultrasonography
   9. Risk Stratification Post Diagnosis
9. Treatment
   1. Systemic Anticoagulation
   2. Reperfusion Treatments
   3. Inferior Vena Cava Filters
   4. Treatment Summary
10. Controversies And Cutting Edge
    1. Computerized Tomographic Pulmonary Angiography Versus Ventilation/Perfusion Scanning
    2. Diagnostic Testing In Pregnancy
11. Disposition
12. Summary
13. Risk Management Pitfalls For Pulmonary Embolism
14. Time- And Cost-Effective Strategies
15. Case Conclusions
16. Clinical Pathway For Suspected Low-Probability Pulmonary Embolism
17. Clinical Pathway For Moderate- To High-Probability Pulmonary Embolism
18. This Month In EM Practice Guidelines Update
19. Tables and Figures
    1. Table 1. Venous Thromboembolic Risk Factors
    2. Table 2. Wells Score
    3. Table 3. Simplified Revised Geneva Score
    4. Table 4. Pulmonary Embolism Rule-Out Criteria (PERC)
    5. Table 5. Sensitivity And Specificity Of Clinical Gestalt, Wells Score, And Revised Geneva Score
    6. Table 6. Clinical Features From The History And Physical Examination That Predict The Presence Or Absence Of Pulmonary Embolism
    7. Table 7. Factors That Can Increase Or Decrease The Accuracy Of The D-dimer Assay In Diagnosing Pulmonary Embolism
    8. Table 8. Accuracy Of sPESI In Predicting 30-Day Mortality Among Different Risk Groups
    9. Table 9. Original And Simplified Pulmonary Embolism Severity Index (PESI)
    10. Figure 1. Electrocardigram Of Patient With Massive Pulmonary Embolism
    11. Figure 2. Association Of Thrombolytic Therapy With A Decrease In Mortality For Unstable Patients With Pulmonary Embolism
20. References

Abstract

Each year in the United States, up to 900,000 individuals will suffer from acute pulmonary embolism, resulting in an estimated 200,000 to 300,000 hospital admissions. Despite decades of research on the topic, the diagnosis remains elusive in many situations and the fatality rate remains significant. This issue presents a review of the current evidence guiding the emergency medicine approach to the diagnosis and treatment of pulmonary embolism. Key to this approach is the concept of risk stratification: using factors from the history and physical examination, plus ancillary tests, to guide clinical decision making. The pathophysiology of pulmonary embolism and decision-support tools are reviewed, and emergency department management strategies are described.

Case Presentations

A 49-year-old male construction worker presents to the ED reporting a brief loss of consciousness 30 minutes prior to arrival while climbing through a crawlspace at work. He reports a prodrome of feeling short of breath, lightheaded, and dizzy, with associated midsternal chest pain. Family members at the bedside report that he was complaining of generalized weakness with mild shortness of breath at rest and on exertion for the past 3 to 4 days. His past medical history is significant for rectal cancer treated with resection, a traumatic fracture of L3, and deep vein thrombosis 9 months ago, after which he completed a 6-month course of warfarin. The patient denies use of tobacco, alcohol consumption, or use of illicit drugs. There is no family history of any medical problems. His vital signs upon arrival are: temperature, 36°C; blood pressure, 104/79 mm Hg; heart rate, 106 beats per minute; respiratory rate, 20 breaths per minute; and oxygen saturation, 95% on room air. He is in no distress, is sitting upright on the stretcher, and is speaking in full sentences. Aside from a regular tachycardia, his exam is normal. Initial ECG shows a sinus tachycardia at 106 beats per minute, rightward axis deviation, ST-segment depressions throughout, and deep T-wave inversions in the anterolateral leads. Laboratory analysis, including cardiac markers, electrolytes, CBC, and renal function are remarkable only for a platelet count of 115,000 x 10⁹/L. Initial cardiac markers and electrolytes are normal. You put acute coronary syndromes on the top of your differential and admit the patient to the observation unit, but you wonder if there is anything else that should be done while waiting for the second troponin...

A short time later, a 58-year-old male with a history of hypertension presents to the ED with leg pain. He woke up 2 days prior with pain and discoloration of his right leg, which has progressively worsened. Although not initially reported in the chief complaint, upon review of systems, the patient reports that he has been dizzy and short of breath for the past couple of days. He denies chest pain, diaphoresis, or syncope. The patient further denies history of coagulopathy or prior blood clots. On exam, he is well-appearing and in no distress. He is afebrile, is tachycardic at 117 beats per minute, is breathing at a rate of 16 breaths per minute, and has a blood pressure of 155/93 mm Hg. His oxygen saturation is 97% on room air. The physical exam is remarkable only for the right lower extremity. The entire right leg is diffusely tender, with edema, erythema, and plethora. Laboratory results are unremarkable; ECG is normal sinus rhythm at a rate of 98 beats per minute with left axis deviation and no ST-segment abnormalities.

Introduction

Each year in the United States, it is estimated that between 600,000 and 900,000 individuals suffer from acute pulmonary embolism (PE), accounting for an estimated 200,000 to 300,000 hospital admissions.^1-4 In the United States, as many as 100,000 deaths are estimated to be caused by venous thromboembolism each year. Furthermore, numerous studies have found that approximately 1% of all patients admitted to hospitals die of acute PE, and an estimated 10% of all hospital deaths are PE related.^5-7 If left untreated, PE can be rapidly fatal.^2,8,9

Improvements in detection and treatment of deep vein thromboses, venous thromboembolism prophylaxis protocols, and improvements in the sensitivity and specificity of diagnostic tests have resulted in a substantially decreased overall mortality from PE in the past decade.^3,10 Nonetheless, despite these advancements, PE still remains a fatal pathology, with a mortality rate of up to 10% of all patients diagnosed with an acute PE in the first 1 to 3 months following diagnosis.^11,12 While the mortality of PE is well publicized, the morbidity associated with undiagnosed PE is not, and it can be very disabling, leading to both pulmonary hypertension and postthrombotic syndrome.^4,13-15 This issue of Emergency Medicine Practice presents a review of the current evidence guiding the emergency medicine approach to the diagnosis and treatment of PE.

Critical Appraisal Of The Literature

An extensive literature search was performed using the PubMed database, Ovid MEDLINE^®, and the Cochrane Database of Systematic Reviews. Searches were limited to the English language. Search terms included, but were not limited to the following: pulmonary embolism, venous thromboembolism, emergency department, treatment, risk stratification, prevention, deep vein thrombosis, and cancer. Search results for pulmonary embolism returned 13,305 articles. The search was further limited to include only clinical trials, meta-analyses, practice guidelines, randomized controlled trials, and reviews, returning 3378 publications. The breadth of the available literature is extensive; thus, clinical trials and guidelines were only reviewed if published within the last decade. The National Guideline Clearinghouse (www.guidelines.gov) and the American College of Emergency Physicians (ACEP) Clinical Policies were referenced for PE management, risk stratification, and prevention guidelines and policies. The bibliographies of these guidelines were also reviewed. A total of 98 references were used in the preparation of this article.

As noted earlier, the number of publications on the topic of PE is extensive, with articles dating back over a century and multiplying exponentially in the last decade. There has been a great expansion in the literature around PE in the last 10 to 20 years. Studies typically focus on either the diagnosis or the treatment of PE, but there are several limitations in the literature regarding both of these types of studies. Diagnostic studies are typically limited by the relatively low prevalence of PE, so maintaining high sensitivity with narrow confidence intervals often requires a multicenter trial in order to enroll enough patients. Nonetheless, several recent meta-analyses have added validity to the findings of smaller studies. An additional limitation for studies regarding the diagnosis of PE is the variability in the definition of a “true negative.” Studies vary widely regarding which “gold standard” (if any) is used to assess if the results of the diagnostic study in question are accurate. “Gold standard” tests vary from clinical follow-up to pulmonary angiography. Regarding treatment studies, the primary limitation is the lack of well-controlled studies in critically ill patients, where poor outcomes are most likely. The challenge of performing informed consent in this group is an important limitation of many studies aiming to evaluate treatment in the critically ill patient with PE. Consequently, studies evaluating the effectiveness of both medical and interventional treatments for those who are the most unstable are often small retrospective studies or large database reviews where the patient populations included in the various studies are difficult to compare or specifics regarding the patients are not available.

Risk Management Pitfalls For Pulmonary Embolism

1. “PE wasn’t a part of this patient’s differential.”

   Consider PE in patients with the most-common complaints (chest pain and shortness of breath), but also with less-common complaints such as syncope, dizziness, or anxiety. PE can present with a multitude of complaints, and it is essential to keep a low threshold when deciding to include it in the differential.

2. “This patient was in shock. I thought he was septic.”

   Always consider massive PE in the differential of undifferentiated atraumatic shock.

3. “Her PERC score was negative, so I didn’t think I had to order any tests.”

   Application of the PERC rule must be confined to a patient population already deemed by the practitioner as low risk. A negative PERC score does not have a negative predictive value high enough to be utilized in any other risk category.

4. “The D-dimer at triage was negative, so I didn’t think I had to worry about PE.”

   Reliance on D-dimer tests other than the quantitative turbidimetric or ELISA assays is inappropriate. Interrater reliability with the qualitative assays used in many point-of-care assays is inadequate, and the sensitivity of this test is not adequate, particularly in the undifferentiated patient.

5. “I knew the quantitative D-dimer test is much better than the bedside assays. Since it was negative, I stopped the work-up there.”

   As with the PERC rule, interpretation of a negative D-dimer assay must be done in the context of the clinician’s pretest probability for disease. Current evidence shows that only in patients considered to have a low clinical risk for PE can a negative quantitative D-dimer safely exclude PE.

6. “The CTPA was negative, so I discharged the patient.”

   As with prior tests mentioned, a negative CTPA (or indeterminate V/Q scan) does not rule out the possibility of PE in a patient considered high risk for emboli. The clinician must interpret the negative results in the context of pretest probability of disease.

7. “I started the heparin, and his vitals were fine, so I admitted him to the floor.”

   A significant percentage of initially stable patients with pulmonary emboli will deteriorate during their hospital course, requiring escalation of therapy. Evaluation of the patient’s potential for deterioration will aid the clinician in admitting the patient to the correct setting.

8. “I held the heparin pending the results of his diagnostic tests. I knew he was really tachycardic,

   but I haven’t confirmed the diagnosis yet.”

   In a patient with a high clinical suspicion for disease and signs of hemodynamic instability, initiate anticoagulation therapy immediately. Delayed treatment is associated with increased mortality in these patients.

9. “I started the patient on 120 mg of enoxaparin. She was dialyzed yesterday.”

   Failure to evaluate for contraindications to specific treatment options can cause significant complications. Patients with renal compromise should be treated with unfractionated heparin. As with all therapeutics, the emergency clinician must have a good understanding of both the indications and contraindications for any therapy initiated.

10. “I know she was stable, but I thought she would benefit from thrombolytics.”

    Although controversy exists regarding the use of thrombolytic therapy in patients with PE, they are not recommended in stable patients, since the risks outweigh the benefits.

Tables and Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study will be included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.

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