Presenting Symptoms Independently Predict Mortality in Septic Shock: Importance of a Previously Unmeasured Confounder.

OBJECTIVES: Presenting symptoms in patients with sepsis may influence rapidity of diagnosis, time-to-antibiotics, and outcome. We tested the hypothesis that vague presenting symptoms are associated with delayed antibiotics and increased mortality. We further characterized individual presenting symptoms and their association with mortality. DESIGN: Retrospective cohort study. SETTING: Emergency department of large, urban, academic U.S. hospital. PATIENTS: All adult patients with septic shock treated in the emergency department between April 2014 and March 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 654 septic shock cases, 245 (37%) presented with vague symptoms. Time-to-antibiotics from first hypotension or elevated lactate was significantly longer for those with vague symptoms versus those with explicit symptoms of infection (1.6 vs 0.8 hr; p < 0.01), and in-hospital mortality was also substantially higher (34% vs 16%; p < 0.01). Patients with vague symptoms were older and sicker as evidenced by triage hypotension, Sequential Organ Failure Assessment score, initial serum lactate, and need for intubation. In multivariate analysis, vague symptoms were independently associated with mortality (adjusted odds ratio, 2.12; 95% CI, 1.32-3.40; p < 0.01), whereas time-to-antibiotics was not associated with mortality (adjusted odds ratio, 1.01; 95% CI, 0.94-1.08; p = 0.78). Of individual symptoms, only the absence of fever, chills, or rigors (odds ratio, 2.70; 95% CI, 1.63-4.47; p < 0.01) and presence of shortness of breath (odds ratio, 1.97; 95% CI, 1.23-3.15; p < 0.01) were independently associated with mortality. CONCLUSIONS: More than one third of patients with septic shock presented to the emergency department with vague symptoms that were not specific to infection. These patients had delayed antibiotic administration and higher risk of mortality even after controlling for demographics, illness acuity, and time-to-antibiotics in multivariate analysis. These findings suggest that the nature of presenting symptoms is an important component of sepsis clinical phenotyping and may be an important confounder in sepsis epidemiologic studies.

Challenges and Opportunities for Emergency Department Sepsis Screening at Triage.

Feasibility of ED triage sepsis screening, before diagnostic testing has been performed, has not been established. In a retrospective, outcome-blinded chart review of a one-year cohort of ED adult septic shock patients ("derivation cohort") and three additional, non-consecutive months of all adult ED visits ("validation cohort"), we evaluated the qSOFA score, the Shock Precautions on Triage (SPoT) vital-signs criterion, and a triage concern-for-infection (tCFI) criterion based on risk factors and symptoms, to screen for sepsis. There were 19,670 ED patients in the validation cohort; 50 developed ED septic shock, of whom 60% presented without triage hypotension, and 56% presented with non-specific symptoms. The tCFI criterion improved specificity without substantial reduction of sensitivity. At triage, sepsis screens (positive qSOFA vital-signs and tCFI, or positive SPoT vital-signs and tCFI) were 28% (95% CI: 16-43%) and 56% (95% CI: 41-70%) sensitive, respectively, p < 0.01. By the conclusion of the ED stay, sensitivities were 80% (95% CI: 66-90%) and 90% (95% CI: 78-97%), p > 0.05, and specificities were 97% (95% CI: 96-97%) and 95% (95% CI: 95-96%), p < 0.001. ED patients who developed septic shock requiring vasopressors often presented normotensive with non-specific complaints, necessitating a low threshold for clinical concern-for-infection at triage.

Classification models to predict vasopressor administration for septic shock in the emergency department.

Optimal management of sepsis and septic shock in the emergency department (ED) involves timely decisions related to intravenous fluid resuscitation and initiation of vasoactive medication support. A decision-support tool trained on electronic health record data, can help improve this complex decision. We retrospectively extracted vital signs, lab measurements, and fluid administration information from 807 patient visits over a two-year period to a major ED. Patients selected for inclusion had a high likelihood of septic shock. We trained binary classifiers to discriminate between patients administered vasopressors in the ED and those not administered vasopressors at any point. Using features extracted from the entire ED visit record yielded a maximum area under the receiver-operating characteristic curve (AUC) of 0.798 (95% CI 0.725-0.849) in a hold-out test set. In a separate task, we used individual vital signs observations with lab results to predict vasopressor administration, yielding a maximum AUC of 0.762 (95% CI 0.748-0.777). Lastly, we trained separate classifiers for different subgroups of vital signs observations. These subgroups were defined by the cumulative number of fluid boluses delivered at the time of the observation. The maximum AUC achieved by any of these classifiers was 0.815 (95% CI 0.784-0.853), occurring for vital signs observations made after 2 bolus administrations. Classifiers in all tasks significantly outperformed existing clinical tools for assessing prognosis in ED sepsis. This work shows how relatively few features can provide instantaneous and accurate prediction of need for an intervention that is typically a complex clinical decision.