Predictors of outcomes in emergency department patients with suspected infections and without fulfillment of the sepsis criteria.

BACKGROUND: Data on patient characteristics and determinants of serious outcomes for acutely admitted patients with infections who do not fulfill the sepsis criteria are sparse. The study aimed to characterize acutely admitted emergency department (ED) patients with infections and a composite outcome of in-hospital mortality or transfer to the intensive care unit without fulfilling the criteria for sepsis and to examine predictors of the composite outcome. METHODS: This was a secondary analysis of data from a prospective observational study of patients with suspected bacterial infection admitted to the ED between October 1, 2017 and March 31, 2018. A National Early Warning Score 2 (NEWS2) ≥ 5 within the first 4 h in the ED was assumed to represent a sepsis-like condition with a high risk for the composite endpoint. Patients who achieved the composite outcome were grouped according to fulfillment of the NEWS2 ≥ 5 criteria. We used logistic regression analysis to estimate the unadjusted and adjusted odds ratio (OR) for the composite endpoint among patients with either NEWS2  < 5 (NEWS2-) or NEWS2  ≥ 5 (NEWS2+). RESULTS: A total of 2055 patients with a median age of 73 years were included. Of these, 198 (9.6%) achieved the composite endpoint, including 59 (29.8%) NEWS2- and 139 (70.2%) NEWS2+ patients, respectively. Diabetes (OR 2.23;1.23-4.0), a Sequential Organ Failure Assessment (SOFA) score ≥ 2 (OR 2.57;1.37-4.79), and a Do-not-attempt-cardiopulmonary-resuscitation order (DNACPR) on admission (OR 3.70;1.75-7.79) were independent predictive variables for the composite endpoint in NEWS2- patients (goodness-of-fit test P = 0.291; area under the receiver operating characteristic curve for the model (AUROC) = 0.72). The regression model for NEWS2+ patients revealed that a SOFA score ≥ 2 (OR 2.79; 1.59-4.91), hypothermia (OR 2.48;1.30-4.75), and DNACPR order on admission were predictive variables for the composite endpoint (goodness-of-fit test P = 0.62; AUROC for the model = 0.70). CONCLUSION: Approximately one-third of the patients with infections and serious outcomes during hospitalization did not meet the NEWS2 threshold for likely sepsis. Our study identified factors with independent predictive values for the development of serious outcomes that should be tested in future prediction models.

National Early Warning Score and New-Onset Atrial Fibrillation for Predicting In-Hospital Mortality or Transfer to the Intensive Care Unit in Emergency Department Patients with Suspected Bacterial Infections.

Purpose: There are conflicting data regarding the role of the National Early Warning Score 2 (NEWS2) in predicting adverse outcomes in patients with infectious diseases. New-onset atrial fibrillation (NO-AF) has been suggested as a sepsis-defining sign of organ dysfunction. This study aimed to examine the prognostic accuracy of NEWS2 and whether NO-AF can provide prognostic information in emergency department (ED) patients with suspected bacterial infections. Patients and Methods: Secondary analyses of data from a prospective observational cohort study of adults admitted in a 6-month period with suspected bacterial infections. We used the composite endpoint of in-hospital mortality or transfer to the intensive care unit as the primary outcome. The prognostic accuracy of NEWS2 and quick sequential organ failure assessment (qSOFA) and covariate-adjusted area under the receiver operating curves (AAUROC) were used to describe the performance of the scores. Logistic regression analysis was used to examine the association between NO-AF and the composite endpoint. Results: A total of 2055 patients were included in this study. The composite endpoint was achieved in 198 (9.6%) patients. NO-AF was observed in 80 (3.9%) patients. The sensitivity and specificity for NEWS2 ≥5 were 70.2% (63.3-76.5) and 60.2% (57.9-62.4), respectively, and those for qSOFA ≥2 were 26.3% (20.3-33.0) and 91.0% (89.6-92.3), respectively. AAUROC for NEWS2 and qSOFA were 0.68 (0.65-0.73) and 0.63 (0.59-0.68), respectively. The adjusted odds ratio for achieving the composite endpoint in 48 patients with NO-AF who fulfilled the NEWS2 ≥5 criteria was 2.71 (1.35-5.44). Conclusion: NEWS2 had higher sensitivity but lower specificity and better, albeit poor, discriminative ability to predict the composite endpoint compared to qSOFA. NO-AF can provide important prognostic information.

Predictors for mortality in patients admitted with suspected bacterial infections - A prospective long-term follow-up study.

OBJECTIVE: The aim was to examine predictors for all-cause mortality in a long-term follow-up study of adult patients with infectious diseases of suspected bacterial origin. METHODS: A prospective observational study of patients admitted to the emergency department during 1.10.2017-31.03.2018. We used Cox regression to estimate adjusted hazard ratios (aHR) with 95% confidence intervals for mortality. RESULTS: A total of 2110 patients were included (median age 73 years). After a median follow-up of 2.1 years 758 (35.9%, 95% CI 33.9-38.0%) patients had died. Age (aHR1.05; 1.04-1.05), male gender (aHR 1.21; 1.17-1.25), cancer (aHR 1.80; 1.73-1.87), misuse of alcohol (aHR 1.30; 1.22-1.38), if admitted with sepsis within the last year before index admission (aHR 1.56;1.50-1.61), a Sequential Organ Failure Assessment (SOFA) score ≥2 (aHR 1.90; 1.83-1.98), SIRS criteria ≥2 (aHR 1.23;1.18-1.28) at admission to the ED, length of stay (aHR 1.05; 1.04-1.05) and devices and implants as sources of infection (aHR 7.0; 5.61-8.73) were independently associated with mortality. Skin infections and increasing haemoblobin values reduced the risk of death. CONCLUSIONS: More than one-third of a population of patients admitted to the emergency department with infectious diseases of suspected bacterial origin had died during a median follow up of 2.1 years. The study identified several independent predictors for mortality.

Microbiological findings in emergency department patients with sepsis identified by the Sepsis-3 criteria: a single-center prospective population-based cohort study.

BACKGROUND: Studies comparing the microbiological profiles among sepsis patients identified with either Sequential Organ Failure Assessment (SOFA) score or systemic inflammatory response syndrome (SIRS) criteria are limited. The aim was to examine if there are differences in the microbiological findings among septic patients identified by Sepsis-3 criteria compared to patients identified by the previous sepsis criteria, SIRS, and without organ failure. A secondary purpose was to examine if we could identify microbiological characteristics with increased risk of 28-day mortality. METHODS: Prospective cohort study of all adult (≥ 18 years) patients admitted with sepsis to the Emergency Department of Slagelse Hospital, Denmark from 1st October 2017 to 31st March 2018. Information regarding microbiological findings was obtained via linkage between a sepsis database and the local microbiological laboratory data system. Data regarding 28-day mortality were obtained from the Danish Civil Registration System. We used logistic regression to estimate the association between specific microbiological characteristics and 28-day mortality. RESULTS: A total of 1616 patients were included; 466 (28.8%; 95% CI 26.6%-31.1%) met SOFA criteria, 398 (24.6%; 95% CI 22.5-26.8%) met SIRS criteria. A total of 127 patients (14.7%; 95% CI 12.4-17.2%) had at least one positive blood culture. SOFA patients had more often positive blood cultures compared to SIRS (13.9% vs. 9.5%; 95 CI on difference 0.1-8.7%). Likewise, Gram-positive bacteria (8.6% vs. 2.8%; 95 CI on difference 2.8-8.8%), infections of respiratory origin (64.8% vs. 57.3%; 95 CI on difference 1.0-14%), Streptococcus pneumoniae (3.2% vs. 1.0%; 95% CI on difference 0.3-4.1) and polymicrobial infections (2.6% vs. 0.3% 95 CI on difference 0.8-3.8%) were more common among SOFA patients. Polymicrobial infections (OR 3.70; 95% CI 1.02-13.40), Staphylococcus aureus (OR 6.30; 95% CI 1.33-29.80) and a pool of "other" microorganisms (OR 3.88; 95% CI 1.34-9.79) in blood cultures were independently associated with mortality. CONCLUSION: Patients identified with sepsis by SOFA score were more often blood culture-positive. Gram-positive pathogens, pulmonary tract infections, Streptococcus pneumoniae, and polymicrobial infections were also more common among SOFA patients. Polymicrobial infection, Staphylococcus aureus, and a group of other organisms were independently associated with an increased risk of death.

Prognostic Accuracy of SOFA, qSOFA, and SIRS for Mortality Among Emergency Department Patients with Infections.

OBJECTIVE: This study aimed to determine the prognostic accuracy of SOFA in comparison to quick-SOFA (qSOFA) and systemic inflammatory response syndrome (SIRS) in predicting 28-day mortality in the emergency department (ED) patients with infections. METHODS: A secondary analysis of data from a prospective study of adult patients with documented or suspected infections admitted to an ED in Denmark from Oct-2017 to Mar-2018. The SOFA scores were calculated after adjustment for chronic diseases. The prognostic accuracy was assessed by analysis of sensitivity, specificity, predictive values, likelihood ratios, and area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI). RESULTS: A total of 2045 patients with a median age of 73.2 (IQR: 60.9-82.1) years were included. The overall 28-day mortality was 7.7%. In patients meeting a SOFA score ≥2, qSOFA score ≥2, and SIRS criteria ≥2 the 28-day mortality was 13.6% (11.2-16.3), 17.8% (12.4-24.3) and 8.3% (6.7-10.2), respectively. SOFA ≥2 had a sensitivity of 61.4% (53.3-69.0) and specificity of 67.3% (65.1-69.4), qSOFA ≥2 had a sensitivity of 19.6% (13.7-26.7) and specificity of 92.4% (91.1-93.6), and SIRS ≥2 had a sensitivity of 52.5% (44.4-60.5) and specificity of 51.5% (49.2-53.7). The AUROC for SOFA compared to SIRS was: 0.68 vs 0.52; p<0.001 and compared to qSOFA: 0.68 vs 0.63; p=0.018. CONCLUSION: A SOFA score of at least two had better prognostic accuracy for 28-day mortality than SIRS and qSOFA. However, the overall accuracy of SOFA was poor for the prediction of 28-day mortality.

Time to administration of antibiotics and mortality in sepsis.

OBJECTIVE: To examine the association between delay of antibiotic treatment and 28-day mortality in a study of septic patients identified by the Sepsis-3 criteria. METHODS: A prospective observational cohort study of patients (≥ 18 years) with sepsis admitted to a Danish emergency department between October 2017 and March 2018. The interval between arrival to the ED and first delivery of antibiotics was used as time to antibiotic treatment (TTA). Logistic regression was used in the analysis of the association between TTA and mortality adjusted for potential confounding. RESULTS: A total of 590 patients, median age 74.2 years, were included. Overall 28-day mortality was 14.6% (95% confidence interval [CI], 11.8-17.7). Median TTA was 4.7 hours (interquartile range 2.7-8.1). The mortality in patients with TTA ≤1 hour was 26.5% (95% CI, 12.8-44.4), and 15.3% (95% CI, 9.8-22.5), 10.5% (95% CI, 6.6-15.8), and 12.8 (95% CI, 7.3-20.1) in the timespans 1-3, 3-6, and 6-9 hours, respectively, and 18.8% (95% CI, 12.0-27.2) in patients with TTA >9 hours. With patients with lowest mortality (TTA timespan 3-6 hours) as reference, the adjusted odds ratio of mortality was 4.53 (95% CI, 1.67-3.37) in patients with TTA ≤1 hour, 1.67 (95% CI, 0.83-3.37) in TTA timespan 1-3 hours, 1.17 (95% CI, 0.56-2.49) in timespan 6-9 hours, and 1.91 (95% CI, 0.96-3.85) in patient with TTA >9 hours. CONCLUSIONS: The adjusted odds of 28-day mortality were lowest in emergency department (ED) patients with sepsis who received antibiotics between 1 and 9 hours and highest in patients treated within 1 and >9 hours after admission to the ED.

Independent predictors for 90-day readmission of emergency department patients admitted with sepsis: a prospective cohort study.

BACKGROUND: The primary objective of our study was to examine predictors for readmission in a prospective cohort of sepsis patients admitted to an emergency department (ED) and identified by the new Sepsis-3 criteria. METHOD: A single-center observational population-based cohort study among all adult (≥18 years) patients with sepsis admitted to the emergency department of Slagelse Hospital during 1.10.2017-31.03.2018. Sepsis was defined as an increase in the sequential organ failure assessment (SOFA) score of ≥2. The primary outcome was 90-day readmission. We followed patients from the date of discharge from the index admission until the end of the follow-up period or until the time of readmission to hospital, emigration or death, whichever came first. We used competing-risks regression to estimate adjusted subhazard ratios (aSHRs) with 95% confidence intervals (CI) for covariates in the regression models. RESULTS: A total of 2110 patients were admitted with infections, whereas 714 (33.8%) suffered sepsis. A total of 52 patients had died during admission and were excluded leaving 662 patients (44.1% female) with a median age of 74.8 (interquartile range: 66.0-84.2) years for further analysis. A total of 237 (35,8%; 95% CI 32.1-39.6) patients were readmitted within 90 days, and 54(8.2%) had died after discharge without being readmitted. We found that a history of malignant disease (aSHR 1,61; 1.16-2.23), if previously admitted with sepsis within 1 year before the index admission (aSHR; 1.41; 1.08-1.84), and treatment with diuretics (aSHR 1.51; 1.17-1.94) were independent predictors for readmission. aSHR (1.49, 1.13-1.96) for diuretic treatment was almost unchanged after exclusion of patients with heart failure, while aSHR (1.47, 0.96-2.25) for malignant disease was slightly attenuated after exclusion of patients with metastatic tumors. CONCLUSIONS: More than one third of patients admitted with sepsis, and discharged alive, were readmitted within 90 days. A history of malignant disease, if previously admitted with sepsis, and diuretic treatment were independent predictors for 90-day readmission.

Prognostic accuracy of qSOFA in predicting 28-day mortality among infected patients in an emergency department: a prospective validation study.

BACKGROUND: Few prospective studies have evaluated the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) criteria in emergency department (ED)settings. The aim of this study was to determine the prognostic accuracy of qSOFA compared with systemic inflammatory response syndrome (SIRS) in predicting the 28-day mortality of infected patients admitted to an ED. METHODS: A prospective observational cohort study of all adult (≥18 years) infected patients admitted to the ED of Slagelse Hospital, Denmark, was conducted from 1 October 2017 to 31 March 2018. Patients were enrolled consecutively and data related to SIRS and qSOFA criteria were obtained from electronic triage record. Information regarding mortality was obtained from the Danish Civil Registration System. The original cut-off values of ≥2 was used to determine the prognostic accuracy of SIRS and qSOFA criteria for predicting 28-day mortality and was assessed by analyses of sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios and area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI). RESULTS: A total of 2112 patients were included in this study. A total of 175 (8.3%) patients met at least two qSOFA criteria, while 1012 (47.9%) met at least two SIRS criteria on admission. A qSOFA criteria of at least two for predicting 28-day mortality had a sensitivity of 19.5% (95% CI 13.6% to 26.5%) and a specificity of 92.6% (95% CI 91.4% to 93.7%). A SIRS criteria of at least two for predicting 28-day mortality had a sensitivity of 52.8% (95% CI 44.8% to 60.8%) and a specificity of 52.5% (95% CI 50.2% to 54.7%). The AUROC values for qSOFA and SIRS were 0.63 (95% CI 0.59 to 0.67) and 0.52 (95% CI 0.48 to 0.57), respectively. CONCLUSION: Both SIRS and qSOFA had poor sensitivity for 28-day mortality. qSOFA improved the specificity at the expense of the sensitivity resulting in slightly higher prognostic accuracy overall.