Effectiveness and Safety of an Emergency Department Code Sepsis Protocol: A Pragmatic Clinical Trial

Abstract

Rationale Sepsis care delivery—including the initiation of prompt, appropriate antimicrobials—remains suboptimal. Objectives This study was conducted to determine direct and off-target effects of emergency department (ED) sepsis care reorganization. Methods This pragmatic pilot trial enrolled adult patients who presented from November 2019 to February 2021 to an ED in Utah before and after implementation of a multimodal, team-based “Code Sepsis” protocol. Patients who presented to two other EDs where usual care was continued served as contemporaneous control subjects. The primary outcome was door-to-antimicrobial time among patients meeting Sepsis-3 criteria before ED departure. Secondary and safety outcomes included all-cause 30-day mortality, antimicrobial utilization and overtreatment, and antimicrobial-associated adverse events. Multivariable regression analyses used difference-in-differences methods to account for trends in outcomes unrelated to the studied intervention. Results Code Sepsis protocol activation ( N = 307) exhibited 8.5% sensitivity and 66% positive predictive value for patients meeting sepsis criteria before ED departure. Among 10,151 patients who met sepsis criteria during the study, adjusted difference-in-differences analysis demonstrated a 13-minute (95% confidence interval = 7–19) decrease in door-to-antimicrobial time associated with Code Sepsis implementation ( P < 0.001). Mortality and clinical safety outcomes were unchanged, but Code Sepsis implementation was associated with increased false-positive presumptive infection diagnoses among patients who met sepsis criteria in the ED and increased antimicrobial utilization. Conclusions Implementation of a team-based protocol for rapid sepsis evaluation and treatment during the coronavirus disease (COVID-19) pandemic’s first year was associated with decreased ED door-to-antimicrobial time but also increased antimicrobial utilization. Measurement of both patient-centered and off-target effects of sepsis care improvement interventions is essential to comprehensive assessment of their value. Clinical trial registered with www.clinicaltrials.gov (NCT 04148989).