Factors and outcomes associated with under- and overdiagnosis of sepsis in the first hour of emergency department care

Abstract

Background: Sepsis remains the leading cause of in-hospital death and one of the costliest inpatient conditions in the United States, while treatment delays worsen outcomes. We sought to determine factors and outcomes associated with a missed emergency physician (EP) diagnosis of sepsis.

Methods: We conducted a secondary analysis of a prospective single-center observational cohort of undifferentiated, critically ill medical patients (September 2020-May 2022). EP gestalt of suspicion for sepsis was measured using a visual analog scale (VAS; 0%-100%) at 15 and 60 min post-patient arrival. The primary outcome was an explicit hospital discharge diagnosis of sepsis that was present on arrival. We calculated test characteristics for clinically relevant subgroups and examined factors associated with initial and persistent missed diagnoses. Associations with process (antibiotics) and clinical (mortality) outcomes were assessed after adjusting for severity.

Results: Among 2484 eligible patients, 275 (11%) met the primary outcome. A VAS score of ≥50 (more likely than not of being septic) at 15 min demonstrated sensitivity 0.83 (95% confidence interval [CI] 0.78-0.87) and specificity 0.85 (95% CI 0.83-0.86). Older age, hypoxia, hypotension, renal insufficiency, leukocytosis, and both high and low temperature were significantly associated with lower accuracy due to reduced specificity, but maintained sensitivity. Of 48 (17%) and 23 (8%) missed cases at 15 and 60 min, elevated lactate, leukocytosis, bandemia, and positive urinalysis were more common in the missed sepsis compared to nonsepsis cases. Missed diagnoses were associated with median (interquartile range) delay of 48 (27-64) min in antibiotic administration but were not independently associated with inpatient mortality as risk ratios remained close to 1 across VAS scores.

Conclusions: This prospective single-academic center study identified patient subgroups at risk of impaired diagnostic accuracy of sepsis, with clinicians often overdiagnosing rather than underdiagnosing these groups. Prompt abnormal laboratory test results can "rescue" initial missed diagnoses, serving as potential clinician- and systems-level intervention points to reduce missed diagnoses. Missed diagnoses delayed antibiotics, but not mortality after controlling for severity of illness.

Keywords: diagnosis; gestalt; misdiagnosis; sepsis.