Jonathan Dreyer

Excluding Pulmonary Embolism at the Bedside without Diagnostic Imaging: Management of Patients with Suspected Pulmonary Embolism Presenting to the Emergency Department by Using a Simple Clinical Model and D-Dimer

Pulmonary embolism is a relatively common disease, with an estimated annual incidence in the United States of 23 cases diagnosed per 100 000 persons (1). More than 50% of cases are undiagnosed. Untreated pulmonary embolism has a high mortality, although risk for death is reduced significantly with anticoagulation (2). Because the clinical signs and symptoms of pulmonary embolism are not specific, timely diagnostic testing must be done to confirm the diagnosis. Ventilation-perfusion lung scanning is the most common imaging procedure for suspected pulmonary embolism. However, the result is frequently nondiagnostic, and additional testing is needed to confirm a diagnosis. Patients presenting to the emergency department with suspected pulmonary embolism present a challenge, particularly if diagnostic testing is not immediately available. We recently validated a simple model (3), which we incorporated into a diagnostic algorithm, to classify pretest probability of pulmonary embolism by using clinical findings along with results on electrocardiography and chest radiography. We had not tested our model or the diagnostic algorithm in an emergency department setting. Another diagnostic test, d-dimer assay, may be useful in patients with suspected pulmonary embolism, but experience with this test to exclude pulmonary embolism diagnoses in an emergency department has been limited [4]. In the current study, we used a diagnostic algorithm based on our clinical model and a non-enzyme-linked immunosorbent d-dimer assay in patients presenting to emergency departments with suspected pulmonary embolism. We sought to 1) demonstrate the safety of excluding the diagnosis of pulmonary embolism in an emergency department using diagnostic algorithms that were based on pretest probability and d-dimer assay results and 2) confirm the reliability of the pretest probability clinical model and d-dimer testing for pulmonary embolism in an emergency department. Methods Patients Data for this study were collected from September 1998 to September 1999 at four participating medical centers in Canada: The Ottawa Civic Hospital, Ottawa, Ontario; the London Health Sciences Centre, London, Ontario; the Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia; and St. Pauls Hospital, Vancouver, British Columbia. The study was approved by the ethics review committees at each of the institutions. Consecutive patients presenting to the emergency departments of the participating centers were eligible if they had suspicion of pulmonary embolism with symptoms for less than 30 days and were experiencing acute onset of new or worsening shortness of breath or chest pain. Exclusion criteria were 1) suspected deep venous thrombosis of the upper extremity as a likely source of pulmonary embolism, 2) no symptoms of pulmonary embolism within 3 days of presentation, 3) anticoagulant therapy for more than 24 hours, 4) expected survival time less than 3 months, 5) contraindication to contrast media, 6) pregnancy, 7) geographic inaccessibility precluding follow-up, or 8) age younger than 18 years. Interventions After giving informed consent, patients were evaluated by 1 of 43 emergency department physicians, who used a simple clinical model to determine the clinical probability of pulmonary embolism (5). The physician assigned points for the following: clinical signs and symptoms of deep venous thrombosis (objectively measured leg swelling and pain with palpation in the deep-vein region), 3.0 points; heart rate higher than 100 beats/min, 1.5 points; immobilization (bedrest, except to access the bathroom, for 3 consecutive days) or surgery in the previous 4 weeks, 1.5 points; previous objectively diagnosed deep venous thrombosis or pulmonary embolism, 1.5 points; hemoptysis, 1.0 point; malignancy (patients with cancer who were receiving treatment, those in whom treatment had been stopped within the past 6 months, or those who were receiving palliative care), 1.0 point; and pulmonary embolism as likely as or more likely than an alternative diagnosis, 3.0 points (5). For the final variable, which was not strictly defined, physicians were told to use the clinical information (obtained by history and physical examination), along with results on chest radiography, electrocardiography, and whatever blood tests were considered necessary to diagnose pulmonary embolism. The pretest probability of pulmonary embolism was considered low in patients whose score was less than 2.0, moderate in patients whose score was at least 2.0 but no higher than 6.0, and high in patients whose score was greater than 6.0. The SimpliRED whole-blood agglutination d-dimer test (AGEN Biomedical, Ltd., Brisbane, Australia) was performed on citrated blood samples in a local coagulation laboratory. In all patients, the d-dimer test was performed only after the clinical model had been applied and the resultant probability had been recorded. Patients were to be managed as outlined in Figure 1. Pulmonary embolism was considered excluded if the patient had been assigned a low clinical pertest probability and had a negative result on d-dimer testing; no imaging procedures were performed in these patients. All other patients had ventilation-perfusion lung scanning. For patients who presented outside normal working hours (between 3:30 p.m. and 7:00 a.m.), a therapeutic dose (200 U/kg of body weight) of the low-molecular-weight heparin Dalteparin (Pharmacia-Upjohn, Mississauga, Ontario, Canada) was given subcutaneously, and diagnostic testing was done in the next 18 hours (6). Dalteparin was given to these patients only after the clinical model was applied and d-dimer testing was done. Figure 1. Diagnostic algorithm for initial evaluation of patients with suspected pulmonary embolism. Ventilation-perfusion scans were interpreted by nuclear medicine physicians who had no knowledge of the clinical model outcome or d-dimer result. The scan interpretations were used to determine patient management. Ventilation-perfusion scans were interpreted as 1) normal, if no perfusion defects were found, 2) high probability, if at least one segmental (or larger) perfusion defect with normal ventilation or at least two large subsegmental perfusion defects [>75% of a segment] with normal ventilation were found, or 3) nondiagnostic, if ventilation-perfusion defects were detected but did not meet the criteria for high probability (7). A lung-segment reference chart was used to interpret ventilation-perfusion scans (8). Compression ultrasonography, when indicated, was performed on both lower extremities from the common femoral vein to the trifurcation of the calf veins, but the calf veins were not examined. Lack of vein compressibility was diagnostic of deep venous thrombosis [9]. In patients with a history of deep venous thrombosis, diagnosis of recurrent thrombus required 1) the noncompressibility on ultrasonography to be in the previously uninvolved extremity or in an area previously unaffected by thrombus or 2) the clot diameter to be more than 4 mm greater than on previous measurement (10). In patients with previous pulmonary embolism, only new defects were considered. Patients were considered to have pulmonary embolism if they had abnormal results on ultrasonography or angiography, a high-probability result on ventilation-perfusion scan, or a venous thromboembolic event during the 3-month follow-up. In all other patients, a diagnosis of pulmonary embolism was considered excluded. Treatment and Follow-up Anticoagulant therapy was withheld in patients in whom a diagnosis of pulmonary embolism was excluded. These patients were given instruction cards and were directed to return at once if they developed new or worsening symptoms or signs suggesting pulmonary embolism or deep venous thrombosis. If at any time venous thromboembolism (deep venous thrombosis or pulmonary embolism) was suspected, patients were studied by using a standardized approach (3). Diagnoses of deep venous thrombosis and pulmonary embolism were excluded if results on ultrasonography and ventilation-perfusion scanning, respectively, were normal. Pulmonary embolism was diagnosed if a new ventilation-perfusion scan showed high probability, and deep venous thrombosis was diagnosed if results on ultrasonography were abnormal. Patients with nondiagnostic scans and equivocal ultrasonography results had gold-standard testing-pulmonary angiography and venography, respectively; the results were evaluated according to previously defined criteria (3). After 3 months, patients were followed up for development of thromboembolic events at a return appointment or by telephone contact. A committee blinded to all patient variables adjudicated suspected outcome events during follow-up. Statistical Analysis Our primary outcome was the proportion of patients who had a venous thromboembolic event during 3-month follow-up among patients in whom the diagnosis of pulmonary embolism had been excluded before follow-up (Figure 1). We and other authors have used this type of outcome in previous studies (3, 11, 12). Our primary analysis was an intention-to-treat analysis of all enrolled patients. We also planned a secondary analysis to evaluate the safety of our strategy in patients in whom the diagnostic algorithm was followed correctly. Because the SimpliRED test can rule out thromboembolism by yielding a negative result, we could also determine the negative predictive values of the d-dimer results in the three pretest-probability groups by determining thromboembolic event rates during the entire study period in those with negative d-dimer results. Before calculating the negative predictive values, we computed the total number of venous thromboembolic events diagnosed during the initial study period (the study period from presentation to follow-up) or follow-up to determine the overall event rates. Then, we determined the negative predictive value by dividing the number of patie

Survival After Application of Automatic External Defibrillators Before Arrival of the Emergency Medical System: Evaluation in the Resuscitation Outcomes Consortium Population of 21 Million

OBJECTIVES The purpose of this study was to assess the effectiveness of contemporary automatic external defibrillator (AED) use. BACKGROUND In the PAD (Public Access Defibrillation) trial, survival was doubled by focused training of lay volunteers to use an AED in high-risk public settings. METHODS We performed a population-based cohort study of persons with nontraumatic out-of-hospital cardiac arrest before emergency medical system (EMS) arrival at Resuscitation Outcomes Consortium (ROC) sites between December 2005 and May 2007. Multiple logistic regression was used to assess the independent association between AED application and survival to hospital discharge. RESULTS Of 13,769 out-of-hospital cardiac arrests, 4,403 (32.0%) received bystander cardiopulmonary resuscitation but had no AED applied before EMS arrival, and 289 (2.1%) had an AED applied before EMS arrival. The AED was applied by health care workers (32%), lay volunteers (35%), police (26%), or unknown (7%). Overall survival to hospital discharge was 7%. Survival was 9% (382 of 4,403) with bystander cardiopulmonary resuscitation but no AED, 24% (69 of 289) with AED application, and 38% (64 of 170) with AED shock delivered. In multivariable analyses adjusting for: 1) age and sex; 2) bystander cardiopulmonary resuscitation performed; 3) location of arrest (public or private); 4) EMS response interval; 5) arrest witnessed; 6) initial shockable or not shockable rhythm; and 7) study site, AED application was associated with greater likelihood of survival (odds ratio: 1.75; 95% confidence interval: 1.23 to 2.50; p < 0.002). Extrapolating this greater survival from the ROC EMS population base (21 million) to the population of the U.S. and Canada (330 million), AED application by bystanders seems to save 474 lives/year. CONCLUSIONS Application of an AED in communities is associated with nearly a doubling of survival after out-of-hospital cardiac arrest. These results reinforce the importance of strategically expanding community-based AED programs.

Implementation of the Canadian C-Spine Rule: prospective 12 centre cluster randomised trial

Objective To evaluate the effectiveness of an active strategy to implement the validated Canadian C-Spine Rule into multiple emergency departments. Design Matched pair cluster randomised trial. Setting University and community emergency departments in Canada. Participants 11 824 alert and stable adults presenting with blunt trauma to the head or neck at one of 12 hospitals. Interventions Six hospitals were randomly allocated to the intervention and six to the control. At the intervention sites, active strategies were used to implement the Canadian C-Spine Rule, including education, policy, and real time reminders on radiology requisitions. No specific intervention was introduced to alter the behaviour of doctors requesting cervical spine imaging at the control sites. Main outcome measure Diagnostic imaging rate of the cervical spine during two 12 month before and after periods. Results Patients were balanced between control and intervention sites. From the before to the after periods, the intervention group showed a relative reduction in cervical spine imaging of 12.8% (95% confidence interval 9% to 16%; 61.7% v 53.3%; P=0.01) and the control group a relative increase of 12.5% (7% to 18%; 52.8% v 58.9%; P=0.03). These changes were significant when both groups were compared (P<0.001). No fractures were missed and no adverse outcomes occurred. Conclusions Implementation of the Canadian C-Spine Rule led to a significant decrease in imaging without injuries being missed or patient morbidity. Final imaging rates were much lower at intervention sites than at most US hospitals. Widespread implementation of this rule could lead to reduced healthcare costs and more efficient patient flow in busy emergency departments worldwide. Trial registration Clinical trials NCT00290875.

Effect of Transport Interval on Out-of-Hospital Cardiac Arrest Survival in the OPALS Study: Implications for Triaging Patients to Specialized Cardiac Arrest Centers

STUDY OBJECTIVE To identify any association between out-of-hospital transport interval and survival to hospital discharge in victims of out-of-hospital cardiac arrest. METHODS Data from the Ontario Prehospital Advanced Life Support Study (January 1, 1991, to December 31, 2002), an Utstein-compliant registry of out-of-hospital cardiac arrest patients from 21 communities, were analyzed. Logistic regression identified factors that were independently associated with survival in consecutive adult, nontraumatic, out-of-hospital cardiac arrest patients and in the subgroup with return of spontaneous circulation. RESULTS A total of 18,987 patients met criteria and 15,559 (81.9%) had complete data for analysis (study group). Return of spontaneous circulation was achieved in 2,299 patients (14.8%), and 689 (4.4%) survived to hospital discharge. Median transport interval was 4.0 minutes (25th quartile 3.0 minutes; 75th quartile 6.2 minutes) for survivors and 4.2 minutes (25th quartile 3.0, 75th quartile 6.2) for nonsurvivors. Logistic regression revealed multiple factors that were independently associated with survival: witnessed arrest (odds ratio 2.61; 95% confidence interval [CI] 2.05 to 3.34), bystander cardiopulmonary resuscitation (odds ratio 2.22; 95% CI 1.82 to 2.70), initial rhythm of ventricular fibrillation/tachycardia (odds ratio 2.22; 95% CI 1.97 to 2.50), and shorter emergency medical services (EMS) response interval (odds ratio 1.26; 95% CI 1.20 to 1.33). There was no association between transport interval and survival in either the study group (odds ratio 1.01; 95% CI 0.99 to 1.05) or the return of spontaneous circulation subgroup (odds ratio 1.04; 95% CI 0.99, 1.08). CONCLUSION In a large out-of-hospital cardiac arrest study from demographically diverse EMS systems, longer transport interval was not associated with decreased survival. Given the growing evidence showing major influence from specialized postarrest care, these findings support conducting clinical trials that assess the effectiveness and safety of bypassing local hospitals to take patients to regional cardiac arrest centers.

The Relationship Between Out-of-Hospital Airway Management and Outcome Among Trauma Patients with Glasgow Coma Scale Scores of 8 or Less

Abstract Background. Airway management remains a fundamental component of optimal care of the severely injured patient, with endotracheal intubation representing the definitive strategy for airway control. However, multiple studies document an association between out-of-hospital intubation and increased mortality for severe traumatic brain injury. Objectives. To explore the relationship between out-of-hospital intubation attempts and outcome among trauma patients with Glasgow Coma Scale (GCS) scores ≤8 across sites participating in the Resuscitation Outcomes Consortium (ROC). Methods. The ROC Epistry–Trauma, an epidemiologic database of prehospital encounters with critically injured trauma victims, was used to identify emergency medical services (EMS)-treated patients with GCS scores ≤8. Multiple logistic regression was used to explore the association between intubation attempts and vital status at discharge, adjusting for the following covariates: age, gender, GCS score, hypotension, mechanism of injury, and ROC site. Sites were then stratified by frequency of intubation attempts and chi-square test for trend was used to associate the frequency of intubation attempts with outcome. Results. A total of 1,555 patients were included in this analysis; intubation was attempted in 758 of these. Patients in whom intubation was attempted had higher mortality (adjusted odds ratio [OR] 2.91, 95% confidence interval [CI] 2.13–3.98, p < 0.01). However, sites with higher rates of attempted intubation had lower mortality across all trauma victims with GCS scores ≤8 (OR 1.40, 95% CI 1.15–1.72, p < 0.01). Conclusions. Patients in whom intubation is attempted have higher adjusted mortality. However, sites with a higher rate of attempted intubation have lower adjusted mortality across the entire cohort of trauma patients with GCS scores ≤8. Key words: prehospital intubation; traumatic brain injury; airway management; paramedic; outcomes; major trauma victim; ventilation; mortality; Glasgow Coma Scale score

Canadian C-Spine Rule study for alert and stable trauma patients: I. Background and rationale

This paper is Part I of a 2-part series to describe the background and methodology for the Canadian C-Spine Rule study to develop a clinical decision rule for rational imaging in alert and stable trauma patients. Current use of radiography is inefficient and variable, in part because there has been a lack of evidence-based guidelines to assist emergency physicians. Clinical decision rules are research-based decision-making tools that incorporate 3 or more variables from the history, physical examination or simple tests. The Canadian CT Head and C-Spine (CCC) Study is a large collaborative effort to develop clinical decision rules for the use of CT head in minor head injury and for the use of cervical spine radiography in alert and stable trauma victims. Part I details the background and rationale for the development of the Canadian C-Spine Rule. Part II will describe in detail the objectives and methods of the Canadian C-Spine Rule study.

The impact of delays to admission from the emergency department on inpatient outcomes

BackgroundWe sought to determine the impact of delays to admission from the Emergency Department (ED) on inpatient length of stay (LOS), and IP cost.MethodsWe conducted a retrospective analysis of 13,460 adult (≥ 18 yrs) ED visits between April 1 2006 and March 30 2007 at a tertiary care teaching hospital with two ED sites in which the mode of disposition was admission to ICU, surgery or inpatient wards. We defined ED Admission Delay as ED time to decision to admit > 12 hours. The primary outcomes were IP LOS, and total IP cost.ResultsApproximately 11.6% (n = 1558) of admitted patients experienced admission delay. In multivariate analysis we found that admission delay was associated with 12.4% longer IP LOS (95% CI 6.6% - 18.5%) and 11.0% greater total IP cost (6.0% - 16.4%). We estimated the cumulative impact of delay on all delayed patients as an additional 2,183 inpatient days and an increase in IP cost of

Differential Survival for Men and Women from Out‐of‐hospital Cardiac Arrest Varies by Age: Results from the OPALS Study

2,109,173 at the study institution.ConclusionsDelays to admission from the ED are associated with increased IP LOS and IP cost. Improving patient flow through the ED may reduce hospital costs and improve quality of care. There may be a business case for investments to reduce emergency department admission delays.

Are reductions in emergency department length of stay associated with improvements in quality of care? A difference-in-differences analysis

BACKGROUND The effect of sex on survival in out-of-hospital cardiac arrest (OHCA) is controversial. Some studies report more favorable outcomes in women, while others suggest the opposite, citing disparities in care. Whether sex predicts differential age-specific survival is still uncertain. OBJECTIVES The objective was to study the sex-associated variation in survival to hospital discharge in OHCA patients as well as the relationship between age and sex for predicting survival. METHODS The Ontario Prehospital Advanced Life Support (OPALS) registry, collected in a large study of rapid defibrillation and advanced life support programs, is Utstein-compliant and has data on OHCA patients (1994 to 2002) from 20 communities in Ontario, Canada. All adult OHCAs not witnessed by emergency medical services (EMS) and treated during one of the three main OPALS phases were included. Clinically significant variables were chosen a priori (age, sex, witnessed arrest, initial cardiopulmonary resuscitation [CPR], shockable rhythm, EMS response interval, and OPALS study phase) and entered into a multivariable logistic regression model with survival to hospital discharge as the outcome, with sex and age as the primary risk factors. Fractional polynomials were used to explore the relationship between age and survival by sex. RESULTS A total of 11,479 (out of 20,695) OPALS cases met inclusion criteria and 10,862 (94.6%) had complete data for regression analysis. As a group, women were older than men (median age = 74 years vs. 69 years, p < 0.01), had fewer witnessed arrests (43% vs. 49%; p < 0.01), had fewer initial ventricular fibrillation/ventricular tachycardia rhythms (24% vs. 42%; p < 0.01), had a lower rate of bystander CPR (12% vs. 17%; p < 0.01), and had lower survival (1.7% vs. 3.2%; p < 0.01). Survival to hospital admission and return of spontaneous circulation did not differ between women and men (p > 0.05). The relationship between age, sex, and survival to hospital discharge could not be analyzed in a single regression model, as age did not have a linear relationship with survival for men, but did for women. Thus, age was kept as a continuous variable for women but was transformed for men using fractional polynomials [ln(age) + age(3) ]. In sex-stratified regression models, the adjusted probability of survival for women decreased as age increased (adjusted odds ratio = 0.88, 95% confidence interval = 0.81 to 0.96, per 5-year increase in age) while for men, the probability of survival initially increased with age until age 65 years and then decreased with increasing age. Women had a higher probability of survival until age 47 years, after which men maintained a higher probability of survival. CONCLUSIONS Overall OHCA survival for women was lower than for men in the OPALS study. Factors related to the sex differences in survival (rates of bystander CPR and shockable rhythms) may be modifiable. The probability of survival differed across age for men and women in a nonlinear fashion. This differential influence of age on survival for men and women should be considered in future studies evaluating survival by sex in OHCA population.

Familiarity with radiation exposure dose from diagnostic imaging for acute pulmonary embolism and current patterns of practice.

Background We sought to determine whether patients seen in hospitals who had reduced overall emergency department (ED) length of stay (LOS) in the 2 years following the introduction of the Ontario Emergency Room Wait Time Strategy were more likely to experience improvements in other measures of ED quality of care for three important conditions. Methods Retrospective medical record review using difference-in-differences analysis to compare changes in performance on quality indicators over the 3-year period between 11 Ontario hospitals where the median ED LOS had improved from fiscal year 2008 to 2010 and 13 matched sites where ED LOS was unchanged or worsened. Patients with acute myocardial infarction (AMI), asthma and paediatric and adult upper limb fractures in these hospitals in 2008 and 2010 were evaluated with respect to 18 quality indicators reflecting timeliness and safety/effectiveness of care in the ED. In a secondary analysis, we examined shift-level ED crowding at the time of the patient visit and performance on the quality indicators. Results Median ED LOS improved by up to 26% (63 min) from 2008 to 2010 in the improved hospitals, and worsened by up to 47% (91 min) in the unimproved sites. We abstracted 4319 and 4498 charts from improved and unimproved hospitals, respectively. Improvement in a hospitals overall median ED LOS from 2008 to 2010 was not associated with a change in any of the other ED quality indicators over the same time period. In our secondary analysis, shift-level crowding was associated only with indicators that reflected timeliness of care. During less crowded shifts, patients with AMI were more likely to be reperfused within target intervals (rate ratio 1.59, 95% CI 1.03 to 2.45), patients with asthma more often received timely administration of steroids (rate ratio 1.88, 95% CI 1.59 to 2.24) and beta-agonists (rate ratio 1.47, 95% CI 1.25 to 1.74), and adult (but not paediatric) patients with fracture were more likely to receive analgesia or splinting within an hour (rate ratio 1.66, 95% CI 1.22 to 2.26). Conclusions These results suggest that a policy approach that targets only reductions in ED LOS is not associated with broader improvements in selected quality measures. At the same time, there is no evidence that efforts to address crowding have a detrimental effect on quality of care.