Christopher Kabrhel

Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism.

Summary.  Overuse of the d‐dimer to screen for possible pulmonary embolism (PE) can have negative consequences. This study derives and tests clinical criteria to justify not ordering a d‐dimer. The test threshold was estimated at 1.8% using the method of Pauker and Kassirer. The PE rule‐out criteria were derived from logistic regression analysis with stepwise backward elimination of 21 variables collected on 3148 emergency department patients evaluated for PE at 10 US hospitals. Eight variables were included in a block rule: Age < 50 years, pulse < 100 bpm, SaO2 > 94%, no unilateral leg swelling, no hemoptysis, no recent trauma or surgery, no prior PE or DVT, no hormone use. The rule was then prospectively tested in a low‐risk group (1427 patients from two hospitals initially tested for PE with a d‐dimer) and a very low‐risk group (convenience sample of 382 patients with chief complaint of dyspnea, PE not suspected). The prevalence of PE was 8% (95% confidence interval: 7–9%) in the low‐risk group and 2% (1–4%) in the very low‐risk group on longitudinal follow‐up. Application of the rule in the low‐risk and very low‐risk populations yielded sensitivities of 96% and 100% and specificities of 27% and 15%, respectively. The prevalence of PE in those who met the rule criteria was 1.4% (0.5–3.0%) and 0% (0–6.2%), respectively. The derived eight‐factor block rule reduced the pretest probability below the test threshold for d‐dimer in two validation populations, but the rules utility was limited by low specificity.

Prospective multicenter evaluation of the pulmonary embolism rule-out criteria

Summary.  Backgound: Over‐investigation of low‐risk patients with suspected pulmonary embolism (PE) represents a growing problem. The combination of gestalt estimate of low suspicion for PE, together with the PE rule‐out criteria [PERC(−): age < 50 years, pulse < 100 beats min−1, SaO2 ≥ 95%, no hemoptysis, no estrogen use, no surgery/trauma requiring hospitalization within 4 weeks, no prior venous thromboembolism (VTE), and no unilateral leg swelling], may reduce speculative testing for PE. We hypothesized that low suspicion and PERC(−) would predict a post‐test probability of VTE(+) or death below 2.0%. Methods: We enrolled outpatients with suspected PE in 13 emergency departments. Clinicians completed a 72‐field, web‐based data form at the time of test order. Low suspicion required a gestalt pretest probability estimate of <15%. The main outcome was the composite of image‐proven VTE(+) or death from any cause within 45 days. Results: We enrolled 8138 patients, 85% of whom had a chief complaint of either dyspnea or chest pain. Clinicians reported a low suspicion for PE, together with PERC(−), in 1666 patients (20%). At initial testing and within 45 days, 561 patients (6.9%, 95% confidence interval 6.5–7.6) were VTE(+), and 56 others died. Among the low suspicion and PERC(−) patients, 15 were VTE(+) and one other patient died, yielding a false‐negative rate of 16/1666 (1.0%, 0.6–1.6%). As a diagnostic test, low suspicion and PERC(−) had a sensitivity of 97.4% (95.8–98.5%) and a specificity of 21.9% (21.0–22.9%). Conclusions: The combination of gestalt estimate of low suspicion for PE and PERC(−) reduces the probability of VTE to below 2% in about 20% of outpatients with suspected PE.

Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double‐blind, placebo‐controlled randomized trial

Acute pulmonary embolism (PE) can worsen quality of life due to persistent dyspnea or exercise intolerance.

Factors Associated With Positive D-dimer Results in Patients Evaluated for Pulmonary Embolism

OBJECTIVES Available D-dimer assays have low specificity and may increase radiographic testing for pulmonary embolism (PE). To help clinicians better target testing, this study sought to quantify the effect of risk factors for a positive quantitative D-dimer in patients evaluated for PE. METHODS This was a prospective, multicenter, observational study. Emergency department (ED) patients evaluated for PE with a quantitative D-dimer were eligible for inclusion. The main outcome of interest was a positive D-dimer. Odds ratio (ORs) and 95% confidence intervals (CIs) were determined by multivariable logistic regression. Adjusted estimates of relative risk were also calculated. RESULTS A total of 4,346 patients had D-dimer testing, of whom 2,930 (67%) were women. A total of 2,500 (57%) were white, 1,474 (34%) were black or African American, 238 (6%) were Hispanic, and 144 (3%) were of other race or ethnicity. The mean (+/-SD) age was 48 (+/-17) years. Overall, 1,903 (44%) D-dimers were positive. Model fit was adequate (c-statistic = 0.739, Hosmer and Lemeshow p-value = 0.13). Significant positive predictors of D-dimer positive included female sex; increasing age; black (vs. white) race; cocaine use; general, limb, or neurologic immobility; hemoptysis; hemodialysis; active malignancy; rheumatoid arthritis; lupus; sickle cell disease; prior venous thromboembolism (VTE; not under treatment); pregnancy and postpartum state; and abdominal, chest, orthopedic, or other surgery. Warfarin use was protective. In contrast, several variables known to be associated with PE were not associated with positive D-dimer results: body mass index (BMI), estrogen use, family history of PE, (inactive) malignancy, thrombophilia, trauma within 4 weeks, travel, and prior VTE (under treatment). CONCLUSIONS Many factors are associated with a positive D-dimer test. The effect of these factors on the usefulness of the test should be considered prior to ordering a D-dimer.

The Massachusetts General Hospital Pulmonary Embolism Response Team (MGH PERT): Creation of a Multidisciplinary Program to Improve Care of Patients With Massive and Submassive Pulmonary Embolism

Abstract New and innovative tools have emerged for the treatment of massive and submassive pulmonary embolism (PE). These novel treatments, when considered alongside existing therapy, such as anticoagulation, systemic intravenous thrombolysis, and open surgical pulmonary embolectomy, have the potential to improve patient outcomes. However, data comparing different treatment modalities are sparse, and guidelines provide only general advice for their use. Treatment decisions rest on clinician expertise and institutional resources. Because various medical and surgical specialties offer different perspectives and expertise, a multidisciplinary approach to patients with massive and submassive PE is required. To address this need, we created a novel multidisciplinary program – the Massachusetts General Hospital (MGH) Pulmonary Embolism Response Team (PERT) – which brings together multiple specialists to rapidly evaluate intermediate- and high-risk patients with PE, formulate a treatment plan, and mobilize the necessary resources to provide the highest level of care. Development of a clinical, educational, and research infrastructure, as well as the creation of a national PERT consortium, will make our experience available to other institutions and serve as a platform for future studies to improve the care of complex patients with massive and submassive PE.

Evaluation of Pulmonary Embolism in the Emergency Department and Consistency With a National Quality Measure: Quantifying the opportunity for improvement

BACKGROUND The National Quality Forum (NQF) has endorsed a performance measure designed to increase imaging efficiency for the evaluation of pulmonary embolism (PE) in the emergency department (ED). To our knowledge, no published data have examined the effect of patient-level predictors on performance. METHODS To quantify the prevalence of avoidable imaging in ED patients with suspected PE, we performed a prospective, multicenter observational study of ED patients evaluated for PE from 2004 through 2007 at 11 US EDs. Adult patients tested for PE were enrolled, with data collected in a standardized instrument. The primary outcome was the proportion of imaging that was potentially avoidable according to the NQF measure. Avoidable imaging was defined as imaging in a patient with low pretest probability for PE, who either did not have a D-dimer test ordered or who had a negative D-dimer test result. We performed subanalyses testing alternative pretest probability cutoffs and imaging definitions on measure performance as well as a secondary analysis to identify factors associated with inappropriate imaging. χ(2) Test was used for bivariate analysis of categorical variables and multivariable logistic regression for the secondary analysis. RESULTS We enrolled 5940 patients, of whom 4113 (69%) had low pretest probability of PE. Imaging was performed in 2238 low-risk patients (38%), of whom 811 had no D-dimer testing, and 394 had negative D-dimer test results. Imaging was avoidable, according to the NQF measure, in 1205 patients (32%; 95% CI, 31%-34%). Avoidable imaging owing to not ordering a D-dimer test was associated with age (odds ratio [OR], 1.15 per decade; 95% CI, 1.10-1.21). Avoidable imaging owing to imaging after a negative D-dimer test result was associated with inactive malignant disease (OR, 1.66; 95% CI, 1.11-2.49). CONCLUSIONS One-third of imaging performed for suspected PE may be categorized as avoidable. Improving adherence to established diagnostic protocols is likely to result in significantly fewer patients receiving unnecessary irradiation and substantial savings.

Clinical features from the history and physical examination that predict the presence or absence of pulmonary embolism in symptomatic emergency department patients: Results of a prospective, multicenter study

STUDY OBJECTIVE Prediction rules for pulmonary embolism use variables explicitly shown to estimate the probability of pulmonary embolism. However, clinicians often use variables that have not been similarly validated, yet are implicitly believed to modify probability of pulmonary embolism. The objective of this study is to measure the predictive value of 13 implicit variables. METHODS Patients were enrolled in a prospective cohort study from 12 centers in the United States; all had an objective test for pulmonary embolism (D-dimer, computed tomographic angiography, or ventilation-perfusion scan). Clinical features including 12 predefined previously validated (explicit) variables and 13 variables not part of existing prediction rules (implicit) were prospectively recorded at presentation. The primary outcome was venous thromboembolism (pulmonary embolism or deep venous thrombosis), diagnosed by imaging up to 45 days after enrollment. Variables with adjusted odds ratios from logistic regression with 95% confidence intervals not crossing unity were considered significant. RESULTS Seven thousand nine hundred forty patients (7.2% venous thromboembolism positive) were enrolled. Mean age was 49 years (standard deviation 17 years) and 67% were female patients. Eight of 13 implicit variables were significantly associated with venous thromboembolism; those with an adjusted odds ratio (OR) greater than 1.5 included non-cancer-related thrombophilia (OR 1.99), pleuritic chest pain (OR 1.53), and family history of venous thromboembolism (OR 1.51). Implicit variables that predicted no venous thromboembolism outcome included substernal chest pain, female sex, and smoking. Nine of 12 explicit variables predicted a positive outcome of venous thromboembolism, including patient history of pulmonary embolism or deep venous thrombosis in the past, unilateral leg swelling, recent surgery, estrogen, hypoxemia, and active malignancy. CONCLUSION In symptomatic outpatients being considered for possible pulmonary embolism, non-cancer-related thrombophilia, pleuritic chest pain, and family history of venous thromboembolism increase probability of pulmonary embolism or deep venous thrombosis. Other variables that are part of existing pretest probability systems were validated as important predictors in this diverse sample of US emergency department patients.

Risk of Thromboembolism Varies, Depending on Category of Immobility in Outpatients

STUDY OBJECTIVE Immobility predisposes to venous thromboembolism, but this risk may vary, depending on the underlying cause of immobility. METHODS This was a prospective, longitudinal outcome study of self-presenting emergency department (ED) patients who were from 12 hospitals and had suspected venous thromboembolism. Using explicit written criteria, clinicians recorded clinical features of each patient in the ED by using a Web-based data form. The form required one of 6 types of immobility: no immobility, general or whole-body immobility greater than 48 hours, limb (orthopedic) immobility, travel greater than 8 hours causing immobility within the previous 7 days, neurologic paralysis, or other immobility not listed above. Patients were followed for 45 days for outcome of venous thromboembolism, which required positive imaging results and clinical plan to treat. Odds ratios (ORs) were derived from logistic regression including 12 covariates. RESULTS From 7,940 patients enrolled, 545 of 7,940 (6.9%) were diagnosed with venous thromboembolism (354 pulmonary embolism, 72 deep venous thrombosis, 119 pulmonary embolism and deep venous thrombosis). Risk of venous thromboembolism varied, depending on immobility type: limb (OR=2.24; 95% confidence interval [CI] 1.40 to 3.60), general (OR=1.76; 95% CI 1.26 to 2.44), other (OR=1.97; 95% CI 1.25 to 3.09), neurologic (OR=2.23; 95% CI 1.01 to 4.92), and travel (OR=1.19; 95% CI 0.85 to 1.67). Other significant risk factors from multivariate analysis included age greater than 50 years (OR =1.5; 95% CI 1.25 to 1.82), unilateral leg swelling (OR=2.68; 95% CI 2.13 to 3.37), previous venous thromboembolism (OR=2.99; 95% CI 2.41 to 3.71), active malignancy (OR=2.23; 95% CI 1.69 to 2.95), and recent surgery (OR=2.12; 95% CI 1.61 to 2.81). CONCLUSION In a large cohort of symptomatic ED patients, risk of venous thromboembolism was substantially increased by presence of limb, whole-body, or neurologic immobility but not by travel greater than 8 hours. These data show the importance of clarifying the cause of immobility in risk assessment of venous thromboembolism.

A Multidisciplinary Pulmonary Embolism Response Team

Correspondence appropriately, but this business model increases the potential for intended or unintended overuse of subsequent interventions. We stand by the statement Dr Lamb and colleagues take issue with: “establishing a discounted rate as a strategy to capture patients...creates a structure that can increase harms from excessive investigation of benign nodules.” 2 The statement is not cited as evidence; it occurs in the discussion of issues regarding screening. We support mak ing screening accessible to those who need it but stand by the opinion that we need the health-care system to appropriately cover the costs of screening (not just the scan itself) with appropriate quality metrics. It would be a poor health policy decision to provide no other structure for lung cancer screening than an inherently confl icted business model with the assumption that it will always turn out to be managed well. We note that our view is consistent with federal policies enacted as part of the Health Insurance Portability and Accountability Act legislation (§ 1128A(a)(5) of the Social Security Act), which forbids gifting services to patients to garner their business. In the absence of a health-care system structure, we support the efforts of institutions, including the laudable example of the Lahey Clinic, to fi nd a way to appropriately implement screening. We believe that clarity about actual costs and potential confl icts is useful in fi nding good ways to manage these issues. We have to be careful because it can be diffi cult to navigate the thin line between superfi cial statements and attractive sound bites that are motivated primarily by a personal agenda and arguments about how it is best for us to proceed with bringing a potential signifi cant health benefi t to those who need it.

Potential Impact of Adjusting the Threshold of the Quantitative D-dimer Based on Pretest Probability of Acute Pulmonary Embolism

OBJECTIVES The utility of D-dimer testing for suspected pulmonary embolism (PE) can be limited by test specificity. The authors tested if the threshold of the quantitative D-dimer can be varied according to pretest probability (PTP) of PE to increase specificity while maintaining a negative predictive value (NPV) of >99%. METHODS This was a prospective, observational multicenter study of emergency department (ED) patients in the United States. Eligible patients had a diagnostic study ordered to evaluate possible PE. PTP was determined by the clinicians unstructured estimate and the Wells score. Five different D-dimer assays were used. D-dimer test performance was measured using 1) standard thresholds and 2) variable threshold values: twice (for low PTP patients), equal (intermediate PTP patients), or half (high PTP patients) of standard threshold. Venous thromboembolism (VTE) within 45 days required positive imaging plus decision to treat. RESULTS The authors enrolled 7,940 patients tested for PE, and clinicians ordered a quantitative D-dimer for 4,357 (55%) patients who had PTPs distributed as follows: low (74%), moderate (21%), or high (4%). At standard cutoffs, across all PTP strata, quantitative D-dimer testing had a test sensitivity of 94% (95% confidence interval [CI] = 91% to 97%), specificity of 58% (95% CI = 56% to 60%), and NPV of 99.5% (95% CI = 99.1% to 99.7%). If variable cutoffs had been used the overall sensitivity would have been 88% (95% CI = 83% to 92%), specificity 75% (95% CI = 74% to 76%), and NPV 99.1% (95% CI = 98.7% to 99.4%). CONCLUSIONS This large multicenter observational sample demonstrates that emergency medicine clinicians currently order a D-dimer in the majority of patients tested for PE, including a large proportion with intermediate PTP and high PTP. Varying the D-dimers cutoff according to PTP can increase specificity with no measurable decrease in NPV.