Abstract & Commentary
Source: Brown MD, et al. An emergency department guideline for the diagnosis of pulmonary embolism: An outcome study. Acad Emerg Med 2005;12:20-25.
This prospective observational study was designed to determine the safety of an emergency department (ED) pulmonary embolism (PE) diagnostic guideline. The study population consisted of all adult patients presenting with clinical suspicion of acute PE during a four-month period. The guideline recommended D-dimer testing in those patients younger than 70 years with a low (less than 20%) clinical suspicion of PE and no unexplained hypoxemia, unilateral leg swelling, recent surgery, hemoptysis, pregnancy, or prolonged duration of symptoms. Diagnostic imaging was recommended for patients having a positive D-dimer (ELISA) >500 ng/mL. For those patients with moderate to high probability of PE, the guideline recommended diagnostic imaging without a D-dimer level. The primary outcome was the identification of venous thromboembolism during a three-month follow-up period. The electronic medical record, telephone contact, questionnaires sent by mail, medical examiner records, and the Social Security Death Index were the sources of follow-up information.
Of 1207 patients evaluated for suspected PE, 71 (5.8%) were diagnosed with venous thromboembolism. There was one missed case of PE on follow-up, for a negative predictive value of 99.9% (95% CI, 99.5% to 100%). There were 677 patients with D-dimers performed and subgroup analysis yielded a sensitivity of 0.93 (95%CI, 0.77 to 0.98) and a specificity of 0.74 (95%CI, 0.70 to 0.77).
Commentary by Stephanie Abbuhl, MD, FACEP
The authors found that the guideline resulted in a negative predictive value (NPV) for PE of 99.9%, and thus, concluded that it is safe and feasible in a community hospital ED. It is possible that one of the reasons the guideline had such a high NPV was the low prevalence of PE in the population tested (only 5.8% overall), lower than in many other studies and much lower than the 20% prevalence the authors estimated to determine their sample size. This should not be mistaken as a negative predictive value of the D-dimer test (only sensitivity and specificity of the D-dimer was calculated). In fact, the sensitivity of the D-dimer was 0.93 with a wide confidence interval that included a lower limit of 0.77. The authors note that in 40 cases the clinician pursued radiographic studies in spite of a negative D-dimer and two (5%) patients had a PE.
A significant limitation of this study is the questionable reliability of the follow-up. As in many outcome studies for PE, the gold standard for ruling out PE—in those patients who did not have an imaging study— was the absence of an identifiable thromboembolic event in the three-month follow-up period. To determine this, the researchers reviewed the Spectrum Health electronic medical records of all 1137 patients. But for the 896 patients who did not confirm that Spectrum Health was their usual source of care, the researchers attempted phone calls and sent letters with only a 52% success rate. County medical examiner’s records were searched for matches of all subjects; when telephone and mail follow-up were both unsuccessful, a search of the Social Security Death Index was performed. The concern is that this follow-up could have missed a significant number of patients who went to another health system with a thromboembolic event.
Before considering implementation of this guideline in your ED, it should be remembered that the guideline only recommended D-dimer testing in patients who were considered by gestalt to be in a low (less than 20%) pretest probability group, who had none of four strong predictors (unexplained hypoxia, unilateral leg swelling, recent surgery or hemoptysis), and who also were younger than 70 years, not pregnant, and did not have a duration of symptoms greater or equal to four days.
Even after this attempt to reduce the false positives and false negatives, the D-dimer test is still far from ideal in its test characteristics and requires a good understanding of its limitations for safe use.
Dr. Abbuhl, Medical Director, Department of Emergency Medicine, The Hospital of the University of Pennsylvania; Associate Professor of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, is on the Editorial Board of Emergency Medicine Alert.