Daniel J. Henning

An Emergency Department Validation of the SEP-3 Sepsis and Septic Shock Definitions and Comparison With 1992 Consensus Definitions

Study objective: The Third International Consensus Definitions Task Force (SEP‐3) proposed revised criteria defining sepsis and septic shock. We seek to evaluate the performance of the SEP‐3 definitions for prediction of inhospital mortality in an emergency department (ED) population and compare the performance of the SEP‐3 definitions to that of the previous definitions. Methods: This was a secondary analysis of 3 prospectively collected, observational cohorts of infected ED subjects aged 18 years or older. The primary outcome was all‐cause inhospital mortality. In accordance with the SEP‐3 definitions, we calculated test characteristics of sepsis (quick Sequential Organ Failure Assessment [qSOFA] score ≥2) and septic shock (vasopressor dependence plus lactate level >2.0 mmol/L) for mortality and compared them to the original 1992 consensus definitions. Results: We identified 7,754 ED patients with suspected infection overall; 117 had no documented mental status evaluation, leaving 7,637 patients included in the analysis. The mortality rate for the overall population was 4.4% (95% confidence interval [CI] 3.9% to 4.9%). The mortality rate for patients with qSOFA score greater than or equal to 2 was 14.2% (95% CI 12.2% to 16.2%), with a sensitivity of 52% (95% CI 46% to 57%) and specificity of 86% (95% CI 85% to 87%) to predict mortality. The original systemic inflammatory response syndrome–based 1992 consensus sepsis definition had a 6.8% (95% CI 6.0% to 7.7%) mortality rate, sensitivity of 83% (95% CI 79% to 87%), and specificity of 50% (95% CI 49% to 51%). The SEP‐3 septic shock mortality was 23% (95% CI 16% to 30%), with a sensitivity of 12% (95% CI 11% to 13%) and specificity of 98.4% (95% CI 98.1% to 98.7%). The original 1992 septic shock definition had a 22% (95% CI 17% to 27%) mortality rate, sensitivity of 23% (95% CI 18% to 28%), and specificity of 96.6% (95% CI 96.2% to 97.0%). Conclusion: Both the new SEP‐3 and original sepsis definitions stratify ED patients at risk for mortality, albeit with differing performances. In terms of mortality prediction, the SEP‐3 definitions had improved specificity, but at the cost of sensitivity. Use of either approach requires a clearly intended target: more sensitivity versus specificity.

Modeling Hourly Resident Productivity in the Emergency Department

Study objective Resident productivity, defined as new patients per hour, carries important implications for emergency department operations. In high‐volume academic centers, essential staffing decisions can be made on the assumption that residents see patients at a static rate. However, it is unclear whether this model mirrors reality; previous studies have not rigorously examined whether productivity changes over time. We examine residents’ productivity across shifts to determine whether it remained consistent. Methods This was a retrospective cohort study conducted in an urban academic hospital with a 3‐year emergency medicine training program in which residents acquire patients ad libitum throughout their shift. Time stamps of all patient encounters were automatically logged. A linear mixed model was constructed to predict productivity per shift hour. Results A total of 14,364 8‐ and 9‐hour shifts were worked by 75 residents between July 1, 2010, and June 20, 2015. This comprised 6,127 (42.7%) postgraduate year (PGY) 1 shifts, 7,236 (50.4%) PGY‐2 shifts, and 998 (6.9%) PGY‐3 nonsupervisory shifts (Table 1). Overall, residents treated a mean of 10.1 patients per shift (SD 3.2), with most patients at Emergency Severity Index level 3 or more acute (93.8%). In the initial hour, residents treated a mean of 2.14 patients (SD 1.2), and every subsequent hour was associated with a significant decrease, with the largest in the second, third, and final hours. Table 1 Characteristics of the study participants and shifts evaluated. Conclusion Emergency medicine resident productivity during a single shift follows a reliable pattern that decreases significantly hourly, a pattern preserved across PGY years and types of shifts. This suggests that resident productivity is a dynamic process, which should be considered in staffing decisions and studied further.

Serum Lactate Predicts Adverse Outcomes in Emergency Department Patients With and Without Infection

Introduction Lactate levels are increasingly used to risk stratify emergency department (ED) patients with and without infection. Whether a serum lactate provides similar prognostic value across diseases is not fully elucidated. This study assesses the prognostic value of serum lactate in ED patients with and without infection to both report and compare relative predictive value across etiologies. Methods We conducted a prospective, observational study of ED patients displaying abnormal vital signs (AVS) (heart rate ≥130 bpm, respiratory rate ≥24 bpm, shock index ≥1, and/or systolic blood pressure <90 mmHg). The primary outcome, deterioration, was a composite of acute renal failure, non-elective intubation, vasopressor administration or in-hospital mortality. Results Of the 1,152 patients with AVS who were screened, 488 patients met the current study criteria: 34% deteriorated and 12.5% died. The deterioration rate was 88/342 (26%, 95% CI: 21 – 30%) for lactate < 2.5 mmol/L, 47/90 (52%, 42 – 63%) for lactate 2.5 – 4.0 mmol/L, and 33/46 (72%, 59 – 85%) for lactate >4.0mmol/L. Trended stratified lactate levels were associated with deterioration for both infected (p<0.01) and non-infected (p<0.01) patients. In the logistic regression models, lactate > 4mmol/L was an independent predictor of deterioration for patients with infection (OR 4.8, 95% CI: 1.7 – 14.1) and without infection (OR 4.4, 1.7 – 11.5). Conclusion Lactate levels can risk stratify patients with AVS who have increased risk of adverse outcomes regardless of infection status.

Initial arterial carbon dioxide tension is associated with neurological outcome after resuscitation from cardiac arrest

STUDY OBJECTIVES To determine the relationships between partial pressure of arterial carbon dioxide (PaCO2), prescribed minute ventilation (MV), and neurologic outcome in patients resuscitated from cardiac arrest. METHODS This was a retrospective cohort study utilizing a multicenter database of adult patients with return of spontaneous circulation (ROSC) after cardiac arrest. The primary outcome was neurologic status at hospital discharge, defined by Cerebral Performance Category (CPC) score: CPC 1-2 was favorable, CPC 3-5 was poor. We compared rates of initial normocarbia (PaCO2 31-49mmHg) and mean sequential PaCO2 measurements obtained over the first 24h. We also assessed the influence of MV on the PaCO2 at initial, 6, 12, 18, and 24h after cardiac arrest using univariate linear regression. RESULTS One hundred and fourteen patients from 3 institutions met inclusion criteria. Overall, 46/114 (40.4%, 95% CI: 31.4-49.4%) patients survived to hospital discharge, and 33/114 (28.9%, 20.6-37.2%) had CPC 1-2 at the time of discharge. A total of 38.9% (95% CI: 29.9-47.9%) of patients had initial normocarbia; 43.2% (28.6-57.8%) of these patients were discharged with CPC 1-2, compared with 20.3% (10.8-29.8%) of dyscarbic patients. By 6h, neurologic outcomes were not significantly associated with PaCO2. Prescribed MV was not associated with PaCO2 at any time point with the exception of a weak correlation at hour 18. CONCLUSION Initial normocarbia was associated with favorable neurological outcome in patients resuscitated from cardiac arrest. This relationship was not seen at subsequent time points. There was no significant association between prescribed MV and PaCO2 or neurologic outcome.

Assessing The Predictive Value of Clinical Factors Used to Determine The Presence of Sepsis Causing Shock in the Emergency Department.

Introduction: Differentiating shock etiologies is a challenging task in the Emergency Department (ED); even the strongest clinical predictors leave some diagnostic uncertainty. This study sought to establish an evidence base for using clinical covariates in the diagnostic evaluation of septic shock. Methods: We conducted a prospective, observational study of consecutive ED patients with shock from November 11, 2012 to September 23, 2013. We included all patients at least 18 years old with shock, defined as new vasopressor requirement, systolic blood pressure less than 90 mmHg after at least 1 L of crystalloid or 2 units packed red blood cells, or systolic blood pressure less than 90 mmHg and fluids withheld due to concern for fluid overload. Multivariate logistic regression and recursive partitioning models were constructed, predicting septic cause of shock. The logistic regression model was derived using first 500 patients, and validated with the subsequent 200 patients. Results: In the derivation cohort, 55.6% (95% confidence interval: 51.2%–60.0%) were septic, and 20.8% (17.2%–24.4%) died during hospitalization. The multivariate model (derivation area under the curve = 0.88, validation area under the curve = 0.89) identified predictors of septic shock, including temperature more than 100.4°F (odds ratio 4.6, 2.3–9.2) and history of fever (odds ratio 9.2, 4.4–19.2); however, only 153 of 277 (55.3%, 49.5%–61.2%) patients with septic shock had either of these findings. In the recursive partitioning model, if all predictors were absent, the probability of sepsis causing shock was 21% (16.6%–25.6%). Conclusions: Clinical data can predict the presence of sepsis causing shock in the ED in most patients. The remaining diagnostic uncertainty provides an opportunity for adding novel diagnostic testing.

The Utility of Inflammatory and Endothelial Markers to Identify Infection in Emergency Department Patients.

Background Identifying infection in emergency department (ED) patients can be challenging. This study assesses the value that inflammatory and endothelial biomarkers add to clinical data when predicting infectious etiologies of abnormal vital signs (AVSs) in ED patients. Methods This study was a prospective, observational cohort study of ED patients with AVSs at an urban, academic tertiary-care hospital, identified from March 1, 2013, to April 15, 2013. Collected blood samples were assayed for soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule 1, vascular cell adhesion molecule 1, plasminogen activator inhibitor 1, interleukin 6, sFlt-1, and procalcitonin. History and physical examination were abstracted from the ED documentation. The primary outcome, infectious etiology, was adjudicated by review of the hospital documentation. Three multivariate logistic regression models predicting infection were created using clinical data, biomarkers, and combined clinical data and biomarker assessments. Integrated discrimination improvement tested the discriminate value of the biomarker and combined models compared with the clinical data model. Results We enrolled 115 patients: 49 determined to have an infection (43%) and 66 without (57%). All biomarkers were significantly associated with infection in univariate analysis. The best clinical model (area under the curve [AUC] = 0.76) included initial temperature (odds ratio [OR], 1.6; confidence interval [CI], 1.1-2.2) and history of fever (OR, 5.0; CI, 1.4-14). The best biomarker model (AUC, 0.82) predicting infection included sE-selectin (OR, 11.0; 95% CI, 1.6-74) and interleukin 6 (OR, 5.1; CI, 2.3-11.6). The combined clinical and biomarker model had an AUC of 0.88, with integrated discrimination improvement = 0.21, compared with the clinical model alone. Conclusion Inflammatory and endothelial markers can improve the clinical identification of infection in ED patients with AVSs.

Goal-Directed Resuscitation in Septic Shock: A Critical Analysis

The Early Goal-Directed Therapy versus Standard Care for Sepsis trial by Rivers and colleagues in 2001 suggested that a significant mortality reduction may be realized through goal-directed interventions early in the care of patients with septic shock. However, the recent publication of the Protocol-Based Care for Early Septic Shock (ProCESS), Australasian Resuscitation in Sepsis Evaluation (ARISE), and Protocolised Management in Sepsis (ProMISE) trials did not demonstrate the superiority of early goal-directed therapy over usual care. If usual care includes timely and meticulous care, a protocol may not be needed to realize the continued lowering mortality rates.

Derivation and Validation of Predictive Factors for Clinical Deterioration after Admission in Emergency Department Patients Presenting with Abnormal Vital Signs Without Shock

Introduction Strategies to identify high-risk emergency department (ED) patients often use markedly abnormal vital signs and serum lactate levels. Risk stratifying such patients without using the presence of shock is challenging. The objective of the study is to identify independent predictors of in-hospital adverse outcomes in ED patients with abnormal vital signs or lactate levels, but who are not in shock. Methods We performed a prospective observational study of patients with abnormal vital signs or lactate level defined as heart rate ≥130 beats/min, respiratory rate ≥24 breaths/min, shock index ≥1, systolic blood pressure <90mm/Hg, or lactate ≥4mmole/L. We excluded patients with isolated atrial tachycardia, seizure, intoxication, psychiatric agitation, or tachycardia due to pain (ie: extremity fracture). The primary outcome was deterioration, defined as development of acute renal failure (creatinine 2× baseline), non-elective intubation, vasopressor requirement, or mortality. Independent predictors of deterioration after hospitalization were determined using logistic regression. Results Of 1,152 consecutive patients identified with abnormal vital signs or lactate level, 620 were excluded, leaving 532 for analysis. Of these, 53/532 (9.9±2.5%) deteriorated after hospital admission. Independent predictors of in-hospital deterioration were: lactate >4.0mmol/L (OR 5.1, 95% CI [2.1–12.2]), age ≥80 yrs (OR 1.9, CI [1.0–3.7]), bicarbonate <21mEq/L (OR 2.5, CI [1.3–4.9]), and initial HR≥130 (OR 3.1, CI [1.5–6.1]). Conclusion Patients exhibiting abnormal vital signs or elevated lactate levels without shock had significant rates of deterioration after hospitalization. ED clinical data predicted patients who suffered adverse outcomes with reasonable reliability.

Evaluating the utility of ST elevation in lead II > lead III in differentiating pericardial disease from STEMI

Background Accurate diagnosis of ST elevation myocardial infarction (STEMI) is complicated by the presence of mimickers such as pericarditis, one of the most common reasons for (negative) emergency cardiac catheterization. Beyond common electrocardiogram (ECG) criteria for pericarditis, a rule of ST segment elevation in lead II greater than lead III (II > III), has been described in literatures and lectures to suggest pericardial disease (PD) and not STEMI. The objective of this study is to define the operating characteristics for the ability of the II > III rule to discriminate PD from STEMI.

A Sepsis-related Diagnosis Impacts Interventions and Predicts Outcomes for Emergency Patients with Severe Sepsis

Introduction Many patients meeting criteria for severe sepsis are not given a sepsis-related diagnosis by emergency physicians (EP). This study 1) compares emergency department (ED) interventions and in-hospital outcomes among patients with severe sepsis, based on the presence or absence of sepsis-related diagnosis, and 2) assesses how adverse outcomes relate to three-hour sepsis bundle completion among patients fulfilling severe sepsis criteria but not given a sepsis-related diagnosis. Methods We performed a retrospective cohort study using patients meeting criteria for severe sepsis at two urban, academic tertiary care centers from March 2015 through May 2015. We included all ED patients with the following: 1) the 1992 Consensus definition of severe sepsis, including two or more systemic inflammatory response syndrome criteria and evidence of organ dysfunction; or 2) physician diagnosis of severe sepsis or septic shock. We excluded patients transferred to or from another hospital and those <18 years old. Patients with an EP-assigned sepsis diagnosis created the “Physician Diagnosis” group; the remaining patients composed the “Consensus Criteria” group. The primary outcome was in-hospital mortality. Secondary outcomes included completed elements of the current three-hour sepsis bundle; non-elective intubation; vasopressor administration; intensive care unit (ICU) admission from the ED; and transfer to the ICU in < 24 hours. We compared proportions of each outcome between groups using the chi-square test, and we also performed a stratified analysis using chi square to assess the association between failure to complete the three-hour bundle and adverse outcomes in each group. Results Of 418 patients identified with severe sepsis we excluded 54, leaving 364 patients for analysis: 121 “Physician Diagnosis” and 243 “Consensus Criteria.” The “Physician Diagnosis” group had a higher in-hospital mortality (12.4% vs 3.3%, P < 0.01) and compliance with the three-hour sepsis bundle (52.1% vs 20.2%, P < 0.01) compared with the “Consensus Criteria” group. An incomplete three-hour sepsis bundle was not associated with a higher incidence of death, intubation, vasopressor use, ICU admission or transfer to the ICU in <24 hours in patients without a sepsis diagnosis. Conclusion “Physician Diagnosis” patients more frequently received sepsis-specific interventions and had a higher incidence of mortality. “Consensus Criteria” patients had infrequent adverse outcomes regardless of three-hour bundle compliance. EPs’ sepsis diagnoses reflect risk-stratification beyond the severe sepsis criteria.