Biomarkers Improve Diagnostics of Sepsis in Adult Patients With Suspected Organ Dysfunction Based on the Quick Sepsis-Related Organ Failure Assessment (qSOFA) Score in the Emergency Department.

OBJECTIVES: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. DESIGN: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. SETTING: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). PATIENTS: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79-0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. CONCLUSIONS: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.

Computed tomography in patients with sepsis presenting to the emergency department: exploring its role in light of patient outcomes.

OBJECTIVES: This study aimed to explore the role of CT in septic patients presenting to the emergency department (ED). MATERIALS AND METHODS: We performed a retrospective secondary analysis of 192 septic patients from a prospective observational study, i.e., the "LIFE POC" study. Sepsis was diagnosed in accordance with the Sepsis-3 definition. Clinical and radiological data were collected from the hospital administration and radiological systems. Information on mortality and morbidity was collected. Time-to-CT between CT scan and sepsis diagnosis (ttCTsd) was calculated. Diagnostic accuracy was assessed with the final sepsis source as reference standard. The reference standard was established through the treating team of the patient based on all available clinical, imaging, and microbiological data. RESULTS: Sixty-two of 192 patients underwent a CT examination for sepsis focus detection. The final septic source was identified by CT in 69.4% (n = 43). CT detected septic foci with 81.1% sensitivity (95% CI, 68.0-90.6%) and 55.6% specificity (95% CI, 21.2-86.3%). Patients with short versus long ttCTsd did not differ in terms of mortality (16.1%, n = 5 vs 9.7, n = 3; p = 0.449), length of hospital stay (median 16 d, IQR 9 d 12 h-23 d 18 h vs median 13 d, IQR 10 d 00 h-24 d 00 h; p = 0.863), or duration of intensive care (median 3d 12 h, IQR 2 d 6 h-7 d 18 h vs median 5d, IQR 2 d-11 d; p = 0.800). CONCLUSIONS: Our findings show a high sensitivity of CT in ED patients with sepsis, confirming its relevance in guiding treatment decisions. The low specificity suggests that a negative CT requires further ancillary diagnostic tests for focus detection. The timing of CT did not affect morbidity or mortality outcomes. CLINICAL RELEVANCE STATEMENT: In patients with sepsis who present to the ED, CT can be used to identify infectious foci on the basis of clinical suspicion, but should not be used as a rule-out test. Scientific evidence for the optimal timing of CT beyond clinical decision-making is currently missing, as potential mortality benefits are clouded by differences in clinical severity at the time of ED presentation. KEY POINTS: • In patients with sepsis who present to the ED, CT for focus identification has a high sensitivity and can thereby be valuable for patient management. • As the specificity is considerably lower, a thorough microbiological assessment is important in these cases. • The timing of CT did not affect morbidity and mortality outcomes in this study, which might be due to variability in clinical severity at the time of ED presentation.

Diagnostic Performance of Procalcitonin for the Early Identification of Sepsis in Patients with Elevated qSOFA Score at Emergency Admission.

Infectious biomarkers such as procalcitonin (PCT) can help overcome the lack of sensitivity of the quick Sequential Organ Failure Assessment (qSOFA) score for early identification of sepsis in emergency departments (EDs) and thus might be beneficial as point-of-care biomarkers in EDs. Our primary aim was to investigate the diagnostic performance of PCT for the early identification of septic patients and patients likely to develop sepsis within 96 h of admission to an ED among a prospectively selected patient population with elevated qSOFA score. In a large multi-centre prospective cohort study, we included all adult patients (n = 742) with a qSOFA score of at least 1 who presented to the ED. PCT levels were measured upon admission. Of the study population 27.3% (n = 202) were diagnosed with sepsis within the first 96 h. The area under the curve for PCT for the identification of septic patients in EDs was 0.86 (95% confidence interval (CI): 0.83-0.89). The resultant sensitivity for PCT at a cut-off of 0.5 µg/L was 63.4% (95% CI: 56.3-70.0). Furthermore, specificity was 89.2% (95% CI: 86.3-91.7), the positive predictive value was 68.8% (95% CI: 62.9-74.2), and the negative predictive value was 86.7% (95% CI: 84.4-88.7). The early measurement of PCT in a patient population with elevated qSOFA score served as an effective tool for the early identification of sepsis in ED patients.

Comparing the validity of different ICD coding abstraction strategies for sepsis case identification in German claims data.

INTRODUCTION: Administrative data are used to generate estimates of sepsis epidemiology and can serve as source for quality indicators. Aim was to compare estimates on sepsis incidence and mortality based on different ICD-code abstraction strategies and to assess their validity for sepsis case identification based on a patient sample not pre-selected for presence of sepsis codes. MATERIALS AND METHODS: We used the national DRG-statistics for assessment of population-level sepsis incidence and mortality. Cases were identified by three previously published International Statistical Classification of Diseases (ICD) coding strategies for sepsis based on primary and secondary discharge diagnoses (clinical sepsis codes (R-codes), explicit coding (all sepsis codes) and implicit coding (combined infection and organ dysfunction codes)). For the validation study, a stratified sample of 1120 adult patients admitted to a German academic medical center between 2007-2013 was selected. Administrative diagnoses were compared to a gold standard of clinical sepsis diagnoses based on manual chart review. RESULTS: In the validation study, 151/937 patients had sepsis. Explicit coding strategies performed better regarding sensitivity compared to R-codes, but had lower PPV. The implicit approach was the most sensitive for severe sepsis; however, it yielded a considerable number of false positives. R-codes and explicit strategies underestimate sepsis incidence by up to 3.5-fold. Between 2007-2013, national sepsis incidence ranged between 231-1006/100,000 person-years depending on the coding strategy. CONCLUSIONS: In the sample of a large tertiary care hospital, ICD-coding strategies for sepsis differ in their accuracy. Estimates using R-codes are likely to underestimate the true sepsis incidence, whereas implicit coding overestimates sepsis cases. Further multi-center evaluation is needed to gain better understanding on the validity of sepsis coding in Germany.

An Early Warning Scoring System to Identify Septic Patients in the Prehospital Setting: The PRESEP Score.

OBJECTIVES: The objective was to develop and evaluate an early sepsis detection score for the prehospital setting. METHODS: A retrospective analysis of consecutive patients who were admitted by emergency medical services (EMS) to the emergency department of the Jena University Hospital was performed. Because potential predictors for sepsis should be based on consensus criteria, the following parameters were extracted from the EMS protocol for further analysis: temperature, heart rate (HR), respiratory rate (RR), oxygen saturation (SaO2 ), Glasgow Coma Scale score, blood glucose, and systolic blood pressure (sBP). Potential predictors were stratified based on inspection of Loess graphs. Backward model selection was performed to select risk factors for the final model. The Prehospital Early Sepsis Detection (PRESEP) score was calculated as the sum of simplified regression weights. Its predictive validity was compared to the Modified Early Warning Score (MEWS), the Robson screening tool, and the BAS 90-30-90. RESULTS: A total of 375 patients were included in the derivation sample; 93 (24.8%) of these had sepsis, including 60 patients with severe sepsis and 12 patients with septic shock. Backward model selection identified temperature, HR, RR, SaO2 , and sBP for inclusion in the PRESEP score. Simplified weights were as follows: temperature > 38°C = 4, temperature < 36°C = 1, HR > 90 beats/min = 2, RR > 22 breaths/min = 1, SaO2 < 92% = 2, and sBP < 90 mm Hg = 2. The cutoff value for a possible existing septic disease based on maximum Youden's index was ≥4 (sensitivity 0.85, specificity 0.86, positive predictive value [PPV] 0.66, and negative predictive value [NPV] 0.95). The area under the receiver operating characteristic curve (AUC) of the PRESEP score was 0.93 (95% confidence interval [CI] = 0.89 to 0.96) and was larger than the AUC of the MEWS (0.93 vs. 0.77, p < 0.001). The PRESEP score surpassed MEWS and BAS 90-60-90 for sensitivity (0.74 and 0.62, respectively), specificity (0.75 and 0.83), PPV (0.45 and 0.51), and NPV (0.91 and 0.89). The Robson screening tool had a higher sensitivity and NPV (0.95 and 0.97), but its specificity and PPV were lower (0.43 and 0.32). CONCLUSIONS: The PRESEP score could be a valuable tool for identifying septic patients in the prehospital setting in the case of suspected infection. It should be prospectively validated.

The effect of antenatal steroid treatment on fetal autonomic heart rate regulation revealed by fetal magnetocardiography (fMCG).

BACKGROUND: Steroid administration to accelerate fetal lung maturation reduces neonatal morbidity and mortality in the case of preterm delivery. Behavioral observations suggest effects on fetal cardiovascular regulation. AIM: We hypothesize that beat to beat heart rate variability (fHRV) derived from fetal magnetocardiography (fMCG) will reveal a direct, acute steroidal effect on fetal autonomic heart rate regulation. SUBJECTS: Eight patients between 29 and 34 weeks of gestation at risk for preterm birth who were treated with betamethasone (2x12 mg within 24 h). STUDY DESIGN: Subjects were studied prior to the first and within 6 h after the second administration. Continuous fMCG was recorded with a 31-channel-SQUID biomagnetometer. Each dataset was processed by subtracting maternal cardiac artefacts and determining the time instants of the fetal heart beats. fHRV analysis was applied to periods of fetal quiescence of 4 min length. OUTCOME MEASURES: We compared fHRV prior versus post steroid administration. RESULTS: Steroid exposure reduced all parameters of overall fHRV significantly. The fHRV parameters representing short term variability remained unaffected. Mean fetal heart rate significantly decreased. The complexity of the heart rate patterns increased. CONCLUSION: Our results suggest an acute shift in the sympatho-vagal balance of fetuses exposed to betamethasone in utero toward sympathetic suppression.