Complex Sepsis Presentations, SEP-1 Compliance, and Outcomes

Abstract

Importance: The Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock Management Bundle (SEP-1) is supported by observational studies that report SEP-1 compliance is associated with lower mortality. Most studies, however, adjusted for limited confounders and provided little insight into why bundle-compliant care was not provided.

Objectives: To identify the clinical factors that complicate the diagnosis and management of sepsis and assess their association with SEP-1 compliance and mortality.

Design, setting, and participants: This retrospective cohort study was conducted among 590 adults with sepsis in the emergency department of 4 academic hospitals from January 1, 2019, to December 31, 2022. Patients' medical records were reviewed between September 2022 and December 2023.

Main outcomes and measures: Study outcomes were (1) characteristics of patients who received SEP-1-compliant care vs characteristics of patients who received noncompliant care and (2) association between SEP-1 compliance and hospital mortality using multivariable models to adjust for successively more potential confounders (first demographics and comorbidities, then infection source, then severity of illness, and then clinical markers of complexity).

Results: Of 590 patients with sepsis (median age, 65 years [IQR, 53-77 years]; 329 men [55.8%]), 335 (56.8%) received SEP-1-compliant care, and 225 (43.2%) received noncompliant care. Compared with patients in the compliant group, patients in the noncompliant group were more likely to be 65 years or older (142 [55.7%] vs 158 [47.2%]; odds ratio [OR], 1.41 [95% CI, 1.01-1.95]), to have multiple comorbidities (Elixhauser score >20: 99 [38.8%] vs 99 [29.6%]; OR, 1.51 [95% CI, 1.07-2.13]), and to have a higher incidence of septic shock (107 [42.0%] vs 107 [31.9%]; OR, 1.54 [95% CI, 1.10-2.16]), kidney dysfunction (87 [34.1%] vs 80 [23.9%]; OR, 1.65 [95% CI, 1.15-2.37]), and thrombocytopenia (43 [16.9%] vs 37 [11.0%]; OR, 1.16 [95% CI, 1.02-2.62]) on presentation. Compared with patients in the compliant group, those in the noncompliant group also had more nonfebrile presentations (136 [53.3%] vs 121 [36.1%]; OR, 2.02 [95% CI, 1.45-2.82]), impaired mental status (92 [36.1%] vs 94 [28.1%]; OR, 1.45 [95% CI, 1.02-2.05]), need for bedside procedures (57 [22.4%] vs 41 [12.2%]; OR, 2.06 [95% CI, 1.33-3.21]), acute concurrent noninfectious illnesses (140 [54.9%] vs 151 [45.1%]; OR, 1.48 [95% CI, 1.07-2.06]), and noninfectious illness as the primary factor associated with their presentation (84 [32.9%] vs 71 [21.2%]; OR, 1.82 [95% CI, 1.08-3.08]). SEP-1 compliance was associated with lower crude mortality rates compared with noncompliance (40 [11.9%] vs 41 [16.1%]; unadjusted OR, 0.60 [95% CI, 0.37-0.98]), but there was no statistically significant difference between groups after successively adjusting for demographics and comorbidities (adjusted OR [AOR], 0.71 [95% CI, 0.42-1.18]), infection source (AOR, 0.71 [95% CI, 0.43-1.20]), severity of illness (AOR, 0.86 [95% CI, 0.50-1.49]), and clinical markers of complexity (AOR, 1.08 [95% CI, 0.61-1.91]).

Conclusions and relevance: In this cohort study of adults with sepsis, complex clinical presentations were more common among patients whose treatment was noncompliant with SEP-1. These nuances are poorly captured in most observational studies but confound the association between SEP-1 compliance and mortality.

Figure 1.. Study Flowchart

SEP-1 indicates Severe Sepsis and Septic Shock Management Bundle. ^aCases from 3 of the hospitals were selected from 2019 to 2021; cases from the fourth hospital were selected from 2020 to 2022. ^bMost cases were commonly transferred from outside the hospital or did not meet the Centers for Medicare & Medicaid Services time zero criteria.

Figure 2.. Comparison of Baseline and Clinical Characteristics in SEP-1–Compliant vs SEP-1–Noncompliant Groups

SI conversion factors: To convert creatinine to micromoles per liter, multiply by 88.4; bilirubin to micromoles per liter, multiply by 17.104; platelets to cells ×10⁹/L, multiply by 1.0; and WBCs to cells ×10⁹/L, multiply by 0.001. ^aStatistically significant differences between the 2 groups.

Figure 3.. Univariable and Maximal Multivariable Analysis for Variables Associated With Hospital Mortality

A, Univariable analysis. “Fever (measured or symptoms)” combines initial measured temperature in the emergency department (ED) or subjective fever, chills, or rigors obtained by history. B, Maximal multivariable analysis. Hospital A is the reference category for the other hospitals (B-D). Statistically significant variables associated with lower mortality are highlighted in light blue; statistically significant variables associated with higher mortality are highlighted in orange. CHF indicates congestive heart failure; DNI, do not intubate; DNR, do not resuscitate; ESKD, end-stage kidney disease; OR, odds ratio; SEP-1, Severe Sepsis and Septic Shock Management Bundle; and WBCs, white blood cells. SI conversion factors: To convert creatinine to micromoles per liter, multiply by 88.4; bilirubin to micromoles per liter, multiply by 17.104; platelets to cells ×10⁹/L, multiply by 1.0; and WBCs to cells ×10⁹/L, multiply by 0.001.

Figure 4.. Association Between SEP-1 Compliance and In-Hospital Death in Multivariable Models Incorporating Successively Detailed Sets of Covariates

Each successive model includes all the previous categories (ie, “Plus clinical markers of complexity” includes baseline characteristics, infection source, and severity of illness). OR indicates odds ratio; SEP-1, Severe Sepsis and Septic Shock Management Bundle.