Contemporary approaches to Pulmonary Embolism Diagnosis - a clinical review.

Introduction: The optimal diagnosis strategy for pulmonary embolism (PE) in the emergency department (ED) remains complex. This review summarizes PE diagnosis with clinical presentation, decision rules and investigations for acute PE. Methods: This review was performed using studies published between January 1, 2010, and September 1, 2023. Results: PE should be considered in ED in patients with chest pain, shortness of breath, syncope or signs of deep veinous thrombosis. Definitive diagnosis of PE relies on thoracic imaging, with the use of CTPA or ventilation/perfusion lung scintigraphy. To limit the continuous increased use of chest imaging, the clinical probability should be the first step for PE work out. The Pulmonary Embolism Rule-out Criteria (PERC rule) can rule out PE at this stage. If not, for low or intermediate probability, several clinical decision rules (CDR) have been validated, either by ruling out PE on clinical signs, or by raising D-Dimer thresholds (YEARS or PEGeD) or by combination of these different rules. It is recommended that patients with a high clinical probability of PE should undergo chest imaging without the need for D-dimer testing. The PE diagnostic approach can be tailored in specific populations such as pregnant, younger, COVID-19, or cancer patients. Conclusion: PE diagnosis workout illustrates the complexity of modern probabilistic-based approaches of decision-making in medicine. It is recommended to use a Bayesian approach with the evaluation of clinical probability, then order D-Dimer if the PERC rule is positive, then adapt the D-Dimer threshold for ordering chest imaging using CDR.

Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis.

AIMS: Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations. METHODS AND RESULTS: An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85-0.89; 95% PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76-0.81). CONCLUSION: The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study. REGISTRATION: PROSPERO ID 89366.

Strategies to mitigate emergency department crowding and its impact on cardiovascular patients.

Emergency department (ED) crowding is a worsening global problem caused by hospital capacity and other health system challenges. While patients across a broad spectrum of illnesses may be affected by crowding in the ED, patients with cardiovascular emergencies-such as acute coronary syndrome, malignant arrhythmias, pulmonary embolism, acute aortic syndrome, and cardiac tamponade-are particularly vulnerable. Because of crowding, patients with dangerous and time-sensitive conditions may either avoid the ED due to anticipation of extended waits, leave before their treatment is completed, or experience delays in receiving care. In this educational paper, we present the underlying causes of crowding and its impact on common cardiovascular emergencies using the input-throughput-output process framework for patient flow. In addition, we review current solutions and potential innovations to mitigate the negative effect of ED crowding on patient outcomes.

Acute Pulmonary Embolism: A Review.

Importance: Pulmonary embolism (PE) is characterized by occlusion of blood flow in a pulmonary artery, typically due to a thrombus that travels from a vein in a lower limb. The incidence of PE is approximately 60 to 120 per 100 000 people per year. Approximately 60 000 to 100 000 patients die from PE each year in the US. Observations: PE should be considered in patients presenting with acute chest pain, shortness of breath, or syncope. The diagnosis is determined by chest imaging. In patients with a systolic blood pressure of at least 90 mm Hg, the following 3 steps can be used to evaluate a patient with possible PE: assessment of the clinical probability of PE, D-dimer testing if indicated, and chest imaging if indicated. The clinical probability of PE can be assessed using a structured score or using clinical gestalt. In patients with a probability of PE that is less than 15%, the presence of 8 clinical characteristics (age <50 years, heart rate <100/min, an oxygen saturation level of > 94%, no recent surgery or trauma, no prior venous thromboembolism event, no hemoptysis, no unilateral leg swelling, and no estrogen use) identifies patients at very low risk of PE in whom no further testing is needed. In patients with low or intermediate clinical probability, a D-dimer level of less than 500 ng/mL is associated with a posttest probability of PE less than 1.85%. In these patients, PE can be excluded without chest imaging. A further refinement of D-dimer threshold is possible in patients aged 50 years and older, and in patients with a low likelihood of PE. Patients with a high probability of PE (ie, >40% probability) should undergo chest imaging, and D-dimer testing is not necessary. In patients with PE and a systolic blood pressure of 90 mm Hg or higher, compared with heparin combined with a vitamin K antagonist such as warfarin followed by warfarin alone, direct oral anticoagulants such as apixaban, edoxaban, rivaroxaban, or dabigatran, are noninferior for treating PE and have a 0.6% lower rate of bleeding. In patients with PE and systolic blood pressure lower than 90 mm Hg, systemic thrombolysis is recommended and is associated with an 1.6% absolute reduction of mortality (from 3.9% to 2.3%). Conclusions and Relevance: In the US, PE affects approximately 370 000 patients per year and may cause approximately 60 000 to 100 000 deaths per year. First-line therapy consists of direct oral anticoagulants such as apixaban, edoxaban, rivaroxaban, or dabigatran, with thrombolysis reserved for patients with systolic blood pressure lower than 90 mm Hg.

Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups : A Systematic Review and Individual-Patient Data Meta-analysis.

BACKGROUND: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. PURPOSE: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. DATA SOURCES: MEDLINE from 1 January 1995 until 1 January 2021. STUDY SELECTION: 16 studies assessing at least 1 diagnostic strategy. DATA EXTRACTION: Individual-patient data from 20 553 patients. DATA SYNTHESIS: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups. LIMITATIONS: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. CONCLUSION: Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. PRIMARY FUNDING SOURCE: Dutch Research Council. (PROSPERO: CRD42018089366).

Prevalence of pulmonary embolism in emergency department patients with isolated syncope: a prospective cohort study.

BACKGROUNDS: Paramount to guide the diagnostic strategy, the prevalence of pulmonary embolism in patients with syncope and no other symptoms is uncertain. We aimed to assess the pulmonary embolism prevalence in patients that present to the emergency department (ED) with syncope and no chest pain nor dyspnea. METHODS: Multicenter prospective cohort study in seven EDs in France. Adult patients who presented to the ED with syncope (transient loss of consciousness) were included. Patients with chest pain or dyspnea were excluded. Included patients underwent formal work-up for pulmonary embolism, including D-dimer testing and further imaging if positive. Cases of pulmonary embolism were adjudicated by two independent expert radiologists with the review of imaging studies. Secondary objectives included the pulmonary embolism prevalence in the subgroup of patients with cancer, in patients with negative Pulmonary Embolism Rule Out criteria (PERC) score, and according to the clinical probability assessed either by Wells or revised Geneva score. RESULTS: We analyzed 411 patients, in whom 128 (31%) underwent a computed tomographic pulmonary angiogram and 9 (2%) a ventilation-perfusion scan. A pulmonary embolism was confirmed in nine patients (prevalence of 2.2%, 95% confidence interval, 1.1-4.3%), including one subsegmental pulmonary embolism. This prevalence was of 18% (3-52%) in patients with cancer and 0.7% (0.1-4%) in PERC negative patients. CONCLUSION: In our sample of patients with isolated syncope, the prevalence of pulmonary embolism was 2.2%. This value is not sufficiently low to negate the requirement for a formal work up in the ED, even in the absence of chest pain or dyspnea. However, the large confidence interval precludes any strong conclusion.

Effect of Systematic Physician Cross-checking on Reducing Adverse Events in the Emergency Department: The CHARMED Cluster Randomized Trial.

Importance: Emergency departments (ED) are environments that are at high risk for medical errors. Previous studies suggested that the proportion of medical errors may decrease when more than 1 physician is involved. Objective: To reduce the proportion of medical errors by implementing systematic cross-checking between emergency physicians. Design, Setting, and Participants: This cluster randomized crossover trial includes a random sample of 14 adult patients (age ≥18 years) per day during two 10-day period in 6 EDs (n = 1680 patients) in France. Interventions: Systematic cross-checking between emergency physicians, 3 times a day, which included a brief presentation of one physician's case to another, followed by the second physician's feedback to the first. Main Outcomes and Measures: Medical error in the ED, defined as an adverse event (either a near miss or a serious adverse event). The primary end point was identified using a 2-level error detection surveillance system, blinded to the strategy allocation. Results: Among the 1680 included patients (mean [SD] age, 57.5 [21.7] years), 144 (8.6%) had an adverse event. There were 54 adverse events among 840 patients (6.4%) in the cross-check group compared with 90 adverse events among 840 patients (10.7%) in the standard care group (relative risk reduction [RRR], 40% [95% CI, 12% to 59%]; absolute risk reduction [ARR], 4.3%; number needed to treat [NNT], 24). There was also a significant reduction rate of near misses (RRR, 47% [95% CI, 15% to 67%]; ARR, 2.7%; NNT, 37) but not of the rate of preventable serious adverse events (RRR, 29% [95% CI, -18% to 57%]; ARR, 1.2%; NNT, 83). Conclusions and Relevance: The implementation of systematic cross-checking between emergency physicians was associated with a significant reduction in adverse events, mainly driven by a reduction in near misses. Trial Registration: ClinicalTrials.gov Identifier: NCT02356926.

The assessment of circulating volume using inferior vena cava collapse index and carotid Doppler velocity time integral in healthy volunteers: a pilot study.

BACKGROUND: Assessment of circulating volume and the requirement for fluid replacement are fundamental to resuscitation but remain largely empirical. Passive leg raise (PLR) may determine fluid responders while avoiding potential fluid overload. We hypothesised that inferior vena cava collapse index (IVCCI) and carotid artery blood flow would change predictably in response to PLR, potentially providing a non-invasive tool to assess circulating volume and identifying fluid responsive patients. METHODS: We conducted a prospective proof of concept pilot study on fasted healthy volunteers. One operator measured IVC diameter during quiet respiration and sniff, and carotid artery flow. Stroke volume (SV) was also measured using suprasternal Doppler. Our primary endpoint was change in IVCCI after PLR. We also studied changes in IVCCI after "sniff", and correlation between carotid artery flow and SV. RESULTS: Passive leg raise was associated with significant reduction in the mean inferior vena cava collapsibility index from 0.24 to 0.17 (p < 0.01). Mean stroke volume increased from 56.0 to 69.2 mL (p < 0.01). There was no significant change in common carotid artery blood flow. Changes in physiology consequent upon passive leg raise normalised rapidly. DISCUSSION: Passive leg raise is associated with a decrease of IVCCI and increase in stroke volume. However, the wide range of values observed suggests that factors other than circulating volume predominate in determining the proportion of collapse with respiration. CONCLUSION: In contrast to other studies, we did not find that carotid blood flow increased with passive leg raise. Rapid normalisation of post-PLR physiology may account for this.

Can transcutaneous carbon dioxide pressure be a surrogate of blood gas samples for spontaneously breathing emergency patients? The ERNESTO experience.

BACKGROUND: It is known that the arterial carbon dioxide pressure (PaCO2) is useful for emergency physicians to assess the severity of dyspnoeic spontaneously breathing patients. Transcutaneous carbon dioxide pressure (PtcCO2) measurements could be a non-invasive alternative to PaCO2 measurements obtained by blood gas samples, as suggested in previous studies. This study evaluates the reliability of a new device in the emergency department (ED). METHODS: We prospectively included patients presenting to the ED with respiratory distress who were breathing spontaneously or under non-invasive ventilation. We simultaneously performed arterial blood gas measurements and measurement of PtcCO2 using a sensor placed either on the forearm or the side of the chest and connected to the TCM4 CombiM device. The agreement between PaCO2 and PtcCO2 was assessed using the Bland-Altman method. RESULTS: Sixty-seven spontaneously breathing patients were prospectively included (mean age 70 years, 52% men) and 64 first measurements of PtcCO2 (out of 67) were analysed out of the 97 performed. Nineteen patients (28%) had pneumonia, 19 (28%) had acute heart failure and 19 (28%) had an exacerbation of chronic obstructive pulmonary disease. Mean PaCO2 was 49 mm Hg (range 22-103). The mean difference between PaCO2 and PtcCO2 was 9 mm Hg (range -47 to +54) with 95% limits of agreement of -21.8 mm Hg and 39.7 mm Hg. Only 36.3% of the measurement differences were within 5 mm Hg. CONCLUSIONS: Our results show that PtcCO2 measured by the TCM4 device could not replace PaCO2 obtained by arterial blood gas analysis.

PERC rule to exclude the diagnosis of pulmonary embolism in emergency low-risk patients: study protocol for the PROPER randomized controlled study.

BACKGROUND: The diagnosis of Pulmonary Embolism (PE) in the emergency department (ED) is crucial. As emergency physicians fear missing this potential life-threatening condition, PE tends to be over-investigated, exposing patients to unnecessary risks and uncertain benefit in terms of outcome. The Pulmonary Embolism Rule-out Criteria (PERC) is an eight-item block of clinical criteria that can identify patients who can safely be discharged from the ED without further investigation for PE. The endorsement of this rule could markedly reduce the number of irradiative imaging studies, ED length of stay, and rate of adverse events resulting from both diagnostic and therapeutic interventions. Several retrospective and prospective studies have shown the safety and benefits of the PERC rule for PE diagnosis in low-risk patients, but the validity of this rule is still controversial. We hypothesize that in European patients with a low gestalt clinical probability and who are PERC-negative, PE can be safely ruled out and the patient discharged without further testing. METHODS/DESIGN: This is a controlled, cluster randomized trial, in 15 centers in France. Each center will be randomized for the sequence of intervention periods: a 6-month intervention period (PERC-based strategy) followed by a 6-month control period (usual care), or in reverse order, with 2 months of "wash-out" between the 2 periods. Adult patients presenting to the ED with a suspicion of PE and a low pre test probability estimated by clinical gestalt will be eligible. The primary outcome is the percentage of failure resulting from the diagnostic strategy, defined as diagnosed venous thromboembolic events at 3-month follow-up, among patients for whom PE has been initially ruled out. DISCUSSION: The PERC rule has the potential to decrease the number of irradiative imaging studies in the ED, and is reported to be safe. However, no randomized study has ever validated the safety of PERC. Furthermore, some studies have challenged the safety of a PERC-based strategy to rule-out PE, especially in Europe where the prevalence of PE diagnosed in the ED is high. The PROPER study should provide high-quality evidence to settle this issue. If it confirms the safety of the PERC rule, physicians will be able to reduce the number of investigations, associated subsequent adverse events, costs, and ED length of stay for patients with a low clinical probability of PE. TRIAL REGISTRATION: NCT02375919 .

Cross-checking to reduce adverse events resulting from medical errors in the emergency department: study protocol of the CHARMED cluster randomized study.

BACKGROUND: Medical errors and preventable adverse events are a major cause of concern, especially in the emergency department (ED) where its prevalence has been reported to be roughly of 5-10% of visits. Due to a short length of stay, emergency patients are often managed by a sole physician - in contrast with other specialties where they can benefit from multiples handover, ward rounds and staff meetings. As some studies report that the rate and severity of errors may decrease when there is more than one physician involved in the management in different settings, we sought to assess the impact of regular systematic cross-checkings between physicians in the ED. DESIGN: The CHARMED (Cross-checking to reduce adverse events resulting from medical errors in the emergency department) study is a multicenter cluster randomized study that aim to evaluate the reduction of the rate of severe medical errors with implementation of systematic cross checkings between emergency physician, compared to a control period with usual care. This study will evaluate the effect of this intervention on the rate of severe medical errors (i.e. preventable adverse events or near miss) using a previously described two-level chart abstraction. We made the hypothesis that implementing frequent and systematic cross checking will reduce the rate of severe medical errors from 10 to 6% - 1584 patients will be included, 140 for each period in each center. DISCUSSION: The CHARMED study will be the largest study that analyse unselected ED charts for medical errors. This could provide evidence that frequent systematic cross-checking will reduce the incidence of severe medical errors. TRIAL REGISTRATION: Clinical Trials, NCT02356926.

Unexpected death within 72 hours of emergency department visit: were those deaths preventable?

INTRODUCTION: We aimed to determine the rate of preventable death in patients who died early and unexpectedly following hospital admission from the emergency department (ED). METHODS: We conducted a retrospective multicenter study in four centers from the Paris metropolitan area. Inclusion criteria were medical patients who died in hospital within 72 hours of ED attendance and were not admitted to the intensive care unit (unexpected death). Exclusion criteria were limitations of care determined by treating physicians. The existence of a limitation of care decision was adjudicated by two independent chart abstractors. Preventable death was defined as death occurring as a result of medical error. For each selected patient with unexpected death, charts were examined for medical errors and rated on a 1 to 5 preventability scale (from very unlikely to very likely) for the preventability of the death. The primary endpoint was the likely preventable death, rated as 4 or 5 on the preventability scale. RESULTS: We retrieved 555 charts; 47 unexpected deaths were analysed; 24 (51%) were considered as preventable. There was a median number of medical errors of two. The most common process breakdowns were incorrect choice of treatment (47% of patients) and failure to order appropriate diagnostic tests (38% of patients). The most common medical error was a severe delay or absence of recommended treatment for severe sepsis, which occurred in 10 (42%) patients. CONCLUSIONS: In our sample, more than half of unexpected deaths are related to a medical error, and could have been prevented.

Unscheduled return visits to the emergency department: consequences for triage.

OBJECTIVES: The objective was to conduct a survey of unscheduled revisits (URs) to the emergency department (ED) within 8 days of a prior visit, to test the hypothesis that patients making these URs are disproportionately likely to suffer short-term mortality or manifest a need for any admission to the hospital (adverse events [AEs]) at the time of the UR, compared to patients triaged at the same level who did not have an unscheduled ED revisit within 8 days. METHODS: This was a 1-year retrospective study of patients with an UR to the ED of an urban, 1,600-bed tertiary care center and teaching hospital. The criteria for inclusion as an UR were: 1) making an emergency visit to our adult ED during 2008, without being admitted to our hospital nor being transferred to another hospital; and 2) subsequently making an UR to the same ED within 8 days following the first one. Patients who were contacted by members of our staff and specifically asked to make return visits to our ED (such as those who returned for wound care follow-up visits), and those who made more than five visits to our ED during 2008, were excluded. AEs were defined as death or hospitalization within 8 days of the second visit. RESULTS: During 2008, there were 946 patients with URs (2% of patients treated and released after the first ED visit), and 931 were analyzed (n = 15 missing values). Associated with the second visit, an AE was noted for 276 (30%) patients. Eight variables were significantly associated with AE: age ≥ 65 years, previously diagnosed cancer, previously diagnosed cardiac disease, previously diagnosed psychiatric disease, presence of a relative at the time of the UR, arrival with a letter from a general practitioner at the time of the UR, a higher level of severity assigned at triage for the UR than for the first ED visit, and having had blood sample analysis performed during the first visit. The median triage score for the UR was not significantly different from that group's median triage score for the first ED visit, whereas the proportion of admissions to the hospital (29%) or to the intensive care unit (ICU; 2%) was greater overall in the UR group than in the patients making their first ED visit. CONCLUSIONS: The authors observed that 2% of patients had an UR. This UR population was at greater risk of AE at the time of their URs compared to their initial visits, but the median triage nurse score was not significantly different between the first visit and the UR. This suggests that the triage score should be systematically upgraded for UR patients.

Factors associated with adverse events resulting from medical errors in the emergency department: two work better than one.

BACKGROUND: The Emergency Department (ED) is an environment at risk for medical errors. OBJECTIVE: Our aim was to determine the factors associated with the adverse events resulting from medical errors in the ED among patients who were admitted. METHODS: This was a prospective observational study. For a 1-month period, we included all ED patients who were subsequently admitted to the medical ward. Detection of medical errors was made by the admitting physician and then validated by two experts who reviewed all available data and medical charts pertaining to the patient's hospital stay, including the first review from the ward physician. Related adverse events resulting from medical errors were then classified by type and severity. Adverse events were defined as medical errors that needed an intervention or caused harm to the patient. Univariate analysis examined relationships between characteristics of both patients and physicians and the risk of adverse events. RESULTS: From 197 analyzed patients, 130 errors were detected, of these, 34 were categorized as adverse events among 19 patients (10%). Seventy-six percent of these were categorized as proficiency errors. The only factors associated with a lower risk of adverse events were the transition of care involving a handoff within the ED (0% vs. 19%; p = 0.03) and the involvement of a resident (junior doctor) in addition to the senior physician (37% vs. 67%; p < 0.01). CONCLUSIONS: In our study, the involvement of more than one physician was associated with a lower risk of adverse events.