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

Ann Am Thorac Soc. 2024 Nov;21(11):1560-1571. doi: 10.1513/AnnalsATS.202403-286OC.

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 (NCT04148989).

Keywords: antibiotic time; emergency medicine; health services; sepsis.

Publication types

  • Pragmatic Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Clinical Protocols
  • Emergency Service, Hospital*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Sepsis* / diagnosis
  • Sepsis* / mortality
  • Sepsis* / therapy
  • Time-to-Treatment
  • Utah

Substances

  • Anti-Bacterial Agents

Associated data

  • ClinicalTrials.gov/NCT04148989