Outcomes Considered Most Important by Emergency Physicians When Determining Disposition of Patients with Pulmonary Embolism

Purpose: Clinical decision rules for the disposition of patients with pulmonary embolism (PE) are typically validated against an outcome of 30-day mortality or disease recurrence. There is little justification for this time frame, nor is it clear whether this outcome reflects emergency department (ED) decision making. Aims: To determine which outcomes emergency physicians (EP) consider most relevant to disposition decisions. Methods: Survey of attending EPs in geographically diverse US states using acute PE as the diagnostic framework. Responses required single-answer multiple choice, a numerical percentage, rank-ordered responses, or a five-point Likert scale. We distributed the survey via e-mail to 608 EPs. Results: We received responses from 292 (48%) EPs: 88% board certified, 91% trained in emergency medicine, and 70% work in academics. Respondents reported discharging 1% of patients with PE from the ED, but 21% reported being asked to do so by an admitting service. EPs were more interested in knowing 5-day (in hospital) outcomes [192/265, 72% (95% exact CI=66%–78%)] than 30-day outcomes [39/261, 15% (95% exact CI=11%–20%)] or 90-day outcomes [29/263, 11% (95% exact CI=8%–15%)]. On a Likert scale, 212/241 (88%, 95% exact CI=83%–92%) agreed or strongly agreed that they considered 5-day (in hospital) clinical deterioration when making a decision to admit or discharge a patient from the ED compared to 184/242 (76%, 95% exact CI=70%–81%) and 73/242 (30%, 95% exact CI=24%–36%) for 30 and 90 days, respectively. A wide variety of clinical outcomes beyond death or recurrent PE were considered indicative of clinical deterioration. Conclusions: Five-day (in hospital) outcomes that incorporate a variety of clinical deterioration events are of interest to EPs when determining the disposition of ED patients with PE. Researchers should consider this when developing and validating clinical decision rules

Prospective Study of the Frequency and Outcomes of Patients with Suspected Pulmonary Embolism Administered Heparin Prior to Confirmatory Imaging

Objectives The administration of empiric systemic anticoagulation (ESA) before confirmatory radiographic testing in patients with suspected pulmonary embolism (PE) may improve outcomes, but no data have been published regarding current practice. We describe the use of ESA in a large prospective cohort of emergency department (ED) patients and report the outcomes of those treated with ESA compared with patients not receiving ESA. Methods 12-center, noninterventional study of ED patients who presented with symptoms concerning for PE. Clinical data including pretest probability and decision to start ESA were recorded at point of care by attending physicians. Patients were followed for adverse in-hospital outcomes and recurrence of venous thromboembolism. Results ESA was initiated 342/7932 (4.3%) of enrolled patients, including 142/618 (23%) patients with high pretest probability. Patients receiving ESA had more abnormal vital signs and were more likely to have a history of venous thromboembolism than those who did not receive ESA. Overall, 481/7,932 (6.1%) had PE diagnosed, 72/481 (15.0%) with PE had ESA, and 72/342 (21%) of ESA patients had PE. Three patients (0.9%, 95%CI: 0.2-2.5%) who received ESA suffered hemorrhagic complications compared with 38 patients (0.5%, 95%CI: 0.4-0.7%) who did not receive ESA. Conclusions In this multicenter sample, ED physicians administered ESA to a small, generally more acutely ill subset of patients with high pretest probability of PE, and very few had hemorrhagic complications. ESA was not associated with any clear difference in outcomes. More study is needed to clarify the risk versus benefit of ESA

Pulmonary embolism: the diagnosis, risk-stratification, treatment and disposition of emergency department patients

The diagnosis or exclusion of pulmonary embolism (PE) remains challenging for emergency physicians. Symptoms can be vague or non-existent, and the clinical presentation shares features with many other common diagnoses. Diagnostic testing is complicated, as biomarkers, like the D-dimer, are frequently false positive, and imaging, like computed tomography pulmonary angiography, carries risks of radiation and contrast dye exposure. It is therefore incumbent on emergency physicians to be both vigilant and thoughtful about this diagnosis. In recent years, several advances in treatment have also emerged. Novel, direct-acting oral anticoagulants make the outpatient treatment of low risk PE easier than before. However, the spectrum of PE severity varies widely, so emergency physicians must be able to risk-stratify patients to ensure the appropriate disposition. Finally, PE response teams have been developed to facilitate rapid access to advanced therapies (e.g., catheter directed thrombolysis) for patients with high-risk PE. This review will discuss the clinical challenges of PE diagnosis, risk stratification and treatment that emergency physicians face every day

Physical inactivity and idiopathic pulmonary embolism in women: prospective study

Objectives To determine the association between physical inactivity (that is, a sedentary lifestyle) and incident idiopathic pulmonary embolism

Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath

BACKGROUND: Many patients have unexplained persistent dyspnea after negative computed tomographic pulmonary angiography (CTPA). We hypothesized that many of these patients have isolated right ventricular (RV) dysfunction from treatable causes. We previously derived a clinical decision rule (CDR) for predicting RV dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of CDR-positive patients had isolated RV dysfunction. Our goal is to validate this previously derived CDR by measuring the prevalence of RV dysfunction and outcomes in dyspneic emergency department patients. METHODS: A secondary analysis of a prospective observational multicenter study that enrolled patients presenting with suspected PE was performed. We included patients with persistent dyspnea, a nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was defined as RV hypokinesis and/or dilation with or without moderate to severe tricuspid regurgitation. RESULTS: A total of 7940 patients were enrolled. Two thousand six hundred sixteen patients were analyzed after excluding patients without persistent dyspnea and those with a significant finding on CTPA. One hundred ninety eight patients had echocardiography performed as standard care. Of those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%) exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with isolated RV dysfunction or overload were more likely than those without RV dysfunction to have a return visit to the emergency department within 45 days for the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). CONCLUSION: This simple clinical prediction rule predicted a 33% prevalence of isolated RV dysfunction or overload. Patients with isolated RV dysfunction had higher recidivism rates and a trend toward worse outcomes

Randomized Trial of Tenecteplase or Placebo with Low Molecular Weight Heparin for Acute Submassive Pulmonary Embolism: Assessment of Patient-Oriented Cardiopulmonary Outcomes at Three Months

Background: Acute submassive pulmonary embolism (PE) with right ventricular (RV) injury and/or concomitant deep venous thrombosis can cause persistent symptoms that degrade quality of life. We tested the hypothesis that intravenous tenecteplase would improve the probability of a favorable outcome at three months after submassive PE. Methods: Multicenter randomized double-blind, placebo controlled trial. Eligible patients were ambulatory at baseline, had image-proven acute PE, a systolic blood pressure > 90 mm Hg and RV dysfunction (abnormal echocardiography, troponin or brain natriuretic peptide). Patients received anticoagulation with low molecular weight heparin (LMWH) and either tiered-dose tenecteplase or saline in an opaque syringe. Composite favorable outcome: 5 day survival to hospital discharge without shock, intubation, or major hemorrhage (any intracranial bleed or need for surgical or medical intervention for acute anemia), and at 90 days, normal RV on resting echocardiography, 6 minute walk distance>330 m, no dyspnea at rest, and no recurrent PE or DVT. Self-perception of wellness was assessed by the SF-16, VEINES-QOL and rank on 1-10 ordinal scale. Results: 83 patients were enrolled, including 33 women, 52 Caucasians, mean age 55+/-14 years, 43 received placebo, 40 received tenecteplase, and 38 had concomittant DVT. A favorable composite outcome occurred in 17/43(40%, 95% CI: 25-56%) treated with placebo, versus 26/40 (65%, 95% CI: 48-79%) treated with tenecteplase, p=0.02 Fisher’s exact. Acute deterioration occurred in 3 patients treated with placebo: fatal PE (1), intubation (1), thrombectomy (1) and in one patient treated with tenecteplase who had a fatal intracranial hemorrhage. At three months, a nonfavorable outcome was found in 23 additional patients treated with placebo, versus 13 patients treated with tenecteplase. Assessments of wellness were consistently higher in the tenecteplase group (e.g., p=0.03 for ordinal scale rank). Conclusions: In this randomized trial, patients with submassive PE treated with LMWH and tenecteplase were more likely to have a favorable patient-oriented outcome at three months than patients treated with LMWH and saline placebo

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, multi-center study

Study Objective—Prediction rules for pulmonary embolism (PE) employ variables explicitly shown to estimate the probability of PE. However, clinicians often use variables that have not been similarly validated, yet are implicitly believed to modify probability of PE. The objective of this study was 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 PE (D-dimer, CT angiography, or V/Q 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 VTE (venous thromboembolism: PE 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—7,940 patients (7.2% VTE+) were enrolled. Mean age was 49±17 years and 67% were female. Eight of 13 implicit variables were significantly associated with VTE; those with an adjusted OR >1.5 included non-cancer related thrombophilia (1.99), pleuritic chest pain (1.53), and family history of VTE (1.51). Implicit variables that predicted no VTE outcome included: substernal chest pain, female gender, and smoking. Nine of 12 explicit variables predicted a positive outcome of VTE, including unilateral leg swelling, recent surgery, estrogen, hypoxemia and active malignancy. Conclusions—In symptomatic outpatients being considered for possible PE, non-cancer related thrombophilia, pleuritic chest pain, and family history of VTE increase probability of PE or DVT. Other variables that are part of existing pretest probability systems were validated as important predictors in this diverse sample of US Emergency department patients

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

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. χ2 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

Contribution of fibrinolysis to the physical component summary of the SF-36 after acute submassive pulmonary embolism

Acute pulmonary embolism (PE) can diminish patient quality of life (QoL). The objective was to test whether treatment with tenecteplase has an independent effect on a measurement that reflects QoL in patients with submassive PE. This was a secondary analysis of an 8-center, prospective randomized controlled trial, utilizing multivariate regression to control for predefined predictors of worsened QoL including: age, active malignancy, history of PE or deep venous thrombosis (DVT), recurrent PE or DVT, chronic obstructive pulmonary disease and heart failure. QoL was measured with the physical component summary (PCS) of the SF-36. Analysis included 76 patients (37 randomized to tenecteplase, 39 to placebo). Multivariate regression yielded an equation f(8, 67), P<0.001, with R2 = 0.303. Obesity had the largest effect on PCS (β = −8.6, P<0.001), with tenecteplase second (β = 4.73, P = 0.056). After controlling for all interactions, tenecteplase increased the PCS by +5.37 points (P = 0.027). In patients without any of the defined comorbidities, the coefficient on the tenecteplase variable was not significant (−0.835, P = 0.777). In patients with submassive PE, obesity had the greatest influence on QoL, followed by use of fibrinolysis. Fibrinolysis had a marginal independent effect on patient QoL after controlling for comorbidities, but was not significant in patients without comorbid conditions