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

RATIONALE: Sepsis care delivery - including initiation of prompt, appropriate antimicrobials - remains suboptimal. OBJECTIVE: Determine direct and off-target effects of emergency department (ED) sepsis care reorganization. METHODS: This pragmatic pilot trial enrolled adult patients presenting November 2019 to February 2021 to an ED in Utah before and after implementation of a multimodal, team-based "Code Sepsis" protocol. Patients presenting to two other EDs where usual care was continued served as contemporaneous controls. 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 employed 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 meeting sepsis criteria during the study, adjusted difference-in-differences analysis demonstrated a 13-minute (95% CI 7-19-minute) 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 diagnosis among patients meeting sepsis criteria in the ED and increased antimicrobial utilization. CONCLUSIONS: Implementation of a team-based protocol for rapid sepsis evaluation and treatment during the 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 REGISTRATION: ClinicalTrials.gov (NCT04148989) This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Concordance Between Initial Presumptive and Final Adjudicated Diagnoses of Infection Among Patients Meeting Sepsis-3 Criteria in the Emergency Department.

BACKGROUND: Guidelines emphasize rapid antibiotic treatment for sepsis, but infection presence is often uncertain at initial presentation. We investigated the incidence and drivers of false-positive presumptive infection diagnosis among emergency department (ED) patients meeting Sepsis-3 criteria. METHODS: For a retrospective cohort of patients hospitalized after meeting Sepsis-3 criteria (acute organ failure and suspected infection including blood cultures drawn and intravenous antimicrobials administered) in 1 of 4 EDs from 2013 to 2017, trained reviewers first identified the ED-diagnosed source of infection and adjudicated the presence and source of infection on final assessment. Reviewers subsequently adjudicated final infection probability for a randomly selected 10% subset of subjects. Risk factors for false-positive infection diagnosis and its association with 30-day mortality were evaluated using multivariable regression. RESULTS: Of 8267 patients meeting Sepsis-3 criteria in the ED, 699 (8.5%) did not have an infection on final adjudication and 1488 (18.0%) patients with confirmed infections had a different source of infection diagnosed in the ED versus final adjudication (ie, initial/final source diagnosis discordance). Among the subset of patients whose final infection probability was adjudicated (n = 812), 79 (9.7%) had only "possible" infection and 77 (9.5%) were not infected. Factors associated with false-positive infection diagnosis included hypothermia, altered mental status, comorbidity burden, and an "unknown infection source" diagnosis in the ED (odds ratio: 6.39; 95% confidence interval: 5.14-7.94). False-positive infection diagnosis was not associated with 30-day mortality. CONCLUSIONS: In this large multihospital study, <20% of ED patients meeting Sepsis-3 criteria had no infection or only possible infection on retrospective adjudication.

Delivery of Lung-protective Ventilation for Acute Respiratory Distress Syndrome: A Hybrid Implementation-Effectiveness Trial.

Rationale: Lung-protective ventilation (LPV) improves outcomes for patients with acute respiratory distress syndrome (ARDS), but adherence remains inadequate. Objectives: To measure the process and clinical impacts of implementation of a science-based intervention to improve LPV adherence for patients with ARDS, in part by increased use of clinical decision support (CDS). Methods: We conducted a type III hybrid implementation/effectiveness pilot trial enrolling adult patients with ARDS admitted to three hospitals before and after the launch of a multimodal implementation intervention to increase the use of mechanical ventilation CDS and improve LPV adherence. The primary outcome was patients' percentage of time adherent to low tidal volume (⩽6.5 ml/kg predicted body weight) ventilation (LTVV). Secondary outcomes included adherence to prescribed oxygenation settings, the use of the CDS tool's independent oxygenation and ventilation components, ventilator-free days, and mortality. Analyses employed multivariable regression to compare adjusted pre- versus postintervention outcomes after the exclusion of a postintervention wash-in period. A sensitivity analysis measured process outcomes' level and trend change postintervention using segmented regression. Results: The 446 included patients had a mean age of 60 years, and 43% were female. Demographic and clinical characteristics were similar pre- versus postintervention. The adjusted proportion of adherent time increased postintervention for LTVV (9.2%; 95% confidence interval [CI], 3.8-14.5%) and prescribed oxygenation settings (11.9%; 95% CI, 7.2-16.5%), as did the probability patients spent ⩾90% of ventilated time on LTVV (adjusted odds ratio [aOR] 2.58; 95% CI, 1.64-4.10) and use of ventilation CDS (aOR, 41.3%; 95% CI, 35.9-46.7%) and oxygenation CDS (aOR, 54.3%; 95% CI, 50.9-57.7%). Ventilator-free days (aOR, 1.15; 95% CI, 0.81-1.62) and 28-day mortality (aOR, 0.78; 95% CI, 0.50-1.20) did not change significantly after intervention. Segmented regression analysis supported a causal relationship between the intervention and improved CDS usage but suggested trends before intervention rather than the studied intervention could explain increased LPV adherence after the intervention. Conclusions: In this pilot trial, a multimodal implementation intervention was associated with increased use of ventilator management CDS for patients with ARDS but was not associated with differences in clinical outcomes and may not have independently caused the observed postintervention improvements in LPV adherence. Clinical trial registered with www.clinicaltrials.gov (NCT03984175).