In the June 2011 issue of the Annals of Emergency Medicine, the American College of Emergency Physicians published a clinical policy focusing on critical issues in the emergency department evaluation and management of adult patients presenting with suspected pulmonary embolism (PE). This is a revision of a clinical policy on suspected PE that was published in 2003.

This clinical policy can also be found on ACEP’s website (www.acep.org) and will be submitted for abstraction on the National Guideline Clearinghouse website (www.guidelines.gov).

This clinical policy takes an evidence-based approach to answering six frequently encountered questions related to emergency department decision making. Recommendations (Level A, B, or C) for patient management are provided based on the strength of evidence using the Clinical Policies Committee’s well-established methodology: Level A recommendations represent patient management principles that reflect a high degree of clinical certainty; Level B recommendations represent patient management principles that reflect moderate clinical certainty; Level C recommendations represent other patient management strategies based on Class III studies, or in the absence of any adequate published literature, based on consensus of the members of the Clinical Policies Committee.

During development, this clinical policy was reviewed and expert review comments were received from individual physicians in the fields of emergency medicine and cardiology, and from individual members of the American College of Chest Physicians, the American College of Radiology, ACEP’s Emergency Ultrasound Section, and ACEP’s Quality and Performance Committee. Their responses were used to refine and enhance this policy further; however, their responses did not imply endorsement of this clinical policy.

It is estimated that 650,000 to 900,000 individuals have pulmonary embolism each year in the United States, resulting in approximately 200,000 deaths. Furthermore, survivors of pulmonary embolism can experience disabling morbidity from pulmonary hypertension or postthrombotic syndrome. Since publication of the 2003 ACEP clinical policy on pulmonary embolism, there have been more than 1,000 publications each year on the subject of pulmonary embolism. The 2011 policy focuses on six critical questions of interest and/or controversy that have developed or still exist since the formulation of the 2003 policy. Due to the strong association between deep vein thrombosis (DVT) and pulmonary embolism, commonly known as venous thromboembolism (VTE) disease, it is difficult to discuss one without the other. For this reason, ACEP has decided to focus on pulmonary embolism and not update the 2003 ACEP policy on deep vein thrombosis.

Question 1: Do objective criteria provide improved risk stratification over gestalt clinical assessment in the evaluation of patients with possible pulmonary embolism?

• Level A recommendations. None specified.
• Level B recommendations. Either objective criteria or gestalt clinical assessment can be used to risk stratify patients with suspected pulmonary embolism. There is insufficient evidence to support the preferential use of one method over another.
• Level C recommendations. None specified.

Estimation of pretest probability is imperative for proper interpretation of tests performed in the evaluation of patients with suspected pulmonary embolism. Pretest probability can be performed by either objective criteria (e.g., Geneva score, Wells Canadian score, Kline Charlotte criteria, Pisa model) or gestalt clinical assessment. With the advent of electronic charting, computer support aides should be developed that will facilitate pretest probability assessment.

Since publication of the 2003 ACEP clinical policy on PE, there have been more than 1,000 publications each year on the subject.

Question 2: What is the utility of the Pulmonary Embolism Rule-out Criteria (PERC) in the evaluation of patients with suspected pulmonary embolism?

• Level A recommendations. None specified.
• Level B recommendations. In patients with a low pretest probability for suspected pulmonary embolism, consider using the PERC to exclude the diagnosis based on historical and physical examination data alone.
• Level C recommendations. None specified.

The D-dimer assay for exclusion of pulmonary embolism has a high sensitivity but poor specificity. As the risks of additional testing in low-risk patients with a false-positive D-dimer may outweigh the benefits, the PERC were developed to select a population at such low risk of pulmonary embolism that D-dimer testing may be unnecessary. In order to be considered PERC negative, the following criteria must be met: age younger than 50 years, pulse rate less than 100 beats/min, SaO2 greater than 94% (at sea level), no unilateral leg swelling, no hemoptysis, no recent trauma or surgery, no previous PE or DVT, and no hormone use. To date, there have been no prospective outcome studies in the use of the PERC for clinical decision making.

Question 3: What is the role of quantitative D-dimer testing in the exclusion of pulmonary embolism?

• Level A recommendations. In patients with a low pretest probability for pulmonary embolism, a negative quantitative D-dimer assay (high sensitivity [e.g., turbidimetric, ELISA]) result can be used to exclude pulmonary embolism.
• Level B recommendations. None specified.
• Level C recommendations. In patients with an intermediate pretest probability for pulmonary embolism, a negative quantitative D-dimer assay (high sensitivity [e.g., turbidimetric, ELISA]) result may be used to exclude pulmonary embolism.

Although the D-dimer assay is not specific, the sensitivity of a negative D-dimer for pulmonary embolism is 93% to 96%. In low-risk patients, studies are consistent in that a negative D-dimer reliably excludes pulmonary embolism. In patients with intermediate pretest probability, studies that included intermediate pretest probability patients within their D-dimer strategy have either not reported the results separately or have had too few patients in this subgroup to draw any firm conclusion. A negative D-dimer should never be utilized to exclude pulmonary embolism in patients with high pretest probability.

Question 4: What is the role of the computed tomography (CT) pulmonary angiogram of the chest as the sole diagnostic test in the exclusion of pulmonary embolism?

• Level A recommendations. None specified.
• Level B recommendations. For patients with a low or pulmonary embolism unlikely (Wells score 4 or less) pretest probability for pulmonary embolism who require additional diagnostic testing (e.g., positive D-dimer result or highly sensitive D-dimer test not available), a negative, multidetector CT pulmonary angiogram alone can be used to exclude pulmonary embolism.
• Level C recommendations. (1) For patients with an intermediate pretest probability for pulmonary embolism and a negative CT pulmonary angiogram result in whom a clinical concern for pulmonary embolism still exists and CT venography has not already been performed, consider additional diagnostic testing (e.g., D-dimer, lower-extremity imaging, ventilation perfusion [VQ] scanning, traditional pulmonary arteriography) prior to exclusion of VTE disease. (2) For patients with a high pretest probability for pulmonary embolism and a negative CT angiogram result, and CT venography has not already been performed, perform additional diagnostic testing (e.g., D-dimer, lower-extremity imaging, VQ scanning, traditional pulmonary arteriography) prior to exclusion of VTE disease.

Note that a negative, highly sensitive, quantitative D-dimer result in combination with a negative multidetector CT pulmonary angiogram result theoretically provides a posttest probability of venous thromboembolism disease less than 1%.

Spiral CT pulmonary angiography, when available, has replaced VQ lung scanning as the principal imaging modality for diagnosing PE in patients without contraindications (e.g., renal insufficiency, contrast allergy). With the technology advancing so rapidly, evidence regarding performance of the newest generation of CT scanners is lacking. Although diagnostic studies report sensitivity in the range of 90% for detection of pulmonary embolism, outcome studies suggest that non-high-risk patients with a negative CT angiogram have very low rates of VTE on 3-month follow-up. The addition of venous imaging either by concurrent CT venogram or by venous ultrasound of the lower extremities results in an incremental increase in sensitivity for detection of VTE disease. Also, high-risk patients with a negative D-dimer and negative CT angiogram have an extremely low rate of VTE on 3-month follow-up. As the reported false-negative rate of CT pulmonary angiogram alone in high-risk patients ranges from 5% to 40%, it is recommended that high-risk patients with a negative CT angiogram undergo additional diagnostic testing prior to ruling out VTE.

Although there has been an explosion of research in PE and in VTE disease, there are still many unanswered questions.

Question 5: What is the role of venous imaging in the evaluation of patients with suspected pulmonary embolism?

• Level A recommendations. None specified.
• Level B recommendations. When a decision is made to perform venous ultrasound as the initial imaging modality, a positive finding in a patient with symptoms consistent with pulmonary embolism can be considered evidence for diagnosis of VTE disease and may preclude the need for additional diagnostic imaging in the emergency department. Examples of situations in which a venous ultrasound may be considered as initial imaging may include patients with obvious signs of DVT for whom venous ultrasound is readily available, patients with relative contraindications for CT scan (e.g., borderline renal insufficiency, CT contrast agent allergy), and pregnant patients.
• Level C recommendations. (1) For patients with an intermediate pretest probability for pulmonary embolism and a negative CT angiogram result, for whom a clinical concern for pulmonary embolism still exists and CT venography has not already been performed, consider lower-extremity venous ultrasound as an additional test to exclude VTE disease (see question 4). (2) In patients with a high pretest probability for pulmonary embolism and a negative CT angiogram, and CT venography has not already been performed, perform additional testing to exclude VTE disease (see question 4). As one of these additional tests, consider lower-extremity venous ultrasound to exclude VTE disease (see question 4).

As discussed in Question 4, it is recommended that high-risk patients with a negative CT angiogram have additional diagnostic testing prior to exclusion of VTE disease. Both venous ultrasound and CT venography have been demonstrated to be reliable modalities. The advantage of CT venography is that it can be performed concurrently with the CT angiography. The advantage of venous ultrasound is that it does not result in any additional radiation exposure to the patient. In select patients with suspected pulmonary embolism in whom it would be advantageous to avoid CT scanning (e.g., renal insufficiency, CT contrast agent allergy, pregnancy), a positive venous ultrasound can be considered diagnostic of VTE disease, thus potentially obviating the need for additional testing.

Question 6. What are the indications for thrombolytic therapy in patients with pulmonary embolism?

• Level A recommendations. None specified.
• Level B recommendations. Administer thrombolytic therapy in hemodynamically unstable patients with confirmed PE for whom the benefits of treatment outweigh the risks of life-threatening bleeding complications. (In centers with the capability for surgical or mechanical thrombectomy, procedural intervention may be used as an alternative therapy.)
• Level C recommendations. (1) Consider thrombolytic therapy in hemodynamically unstable patients with a high clinical suspicion for pulmonary embolism for whom the diagnosis of PE cannot be confirmed in a timely manner. (2) At this time, there is insufficient evidence to make any recommendations regarding use of thrombolytics in any subgroup of hemodynamically stable patients. Thrombolytics have been shown to result in faster improvements in right ventricular function and pulmonary perfusion, but these benefits have not translated to improvements in mortality.
  Despite proven benefit of thrombolytic therapy in patients with ST-segment elevation acute myocardial infarction and select patients with acute strokes, indications for use of thrombolytic therapy in patients with pulmonary embolism remain controversial despite more than 40 years of experience. Overwhelming consensus opinion is to treat hemodynamically unstable patients with confirmed PE when the benefits of treatment outweigh the risks. As it is doubtful that any randomized study in the treatment of hemodynamically unstable patients will ever be performed, future studies should focus on the hemodynamically stable patients at higher risk of adverse outcome.
  Although there has been an explosion of research in pulmonary embolism and in VTE disease, there are still many unanswered questions. With the advent of electronic charting, studies must be performed integrating decision support tools that utilize pretest probability assessment with standardized algorithms in order to make the best use of the available diagnostic and treatment modalities. Outcome studies are also needed that investigate the utility of the newest generation of CT scanners that have much higher resolution than the 4- to 64-channel detectors utilized in the studies that form the basis of the recommendations in this clinical policy. Finally, randomized studies investigating which populations of hemodynamically stable patients with diagnosed pulmonary embolism will benefit from thrombolytic therapy must be performed. The Pulmonary Embolism Thrombolysis Study (PEITHO) is an ongoing randomized, controlled trial of tenecteplase versus placebo in pulmonary embolism patients with right ventricular dysfunction on echocardiography and an elevated troponin level. It is hoped that this study will identify a specific subgroup who will benefit from thrombolytic therapy.

Dr. Fesmire is Professor and Clinical Research Director in the Department of Emergency Medicine, University of Tennessee College of Medicine Chattanooga; and Medical Director of the Chest Pain Center, Erlanger Medical Center, Chattanooga.