The Effect of Severe Sepsis and Septic Shock Management Bundle (SEP-1) Compliance and Implementation on Mortality Among Patients With Sepsis : A Systematic Review

Abstract

Background: The Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock Management Bundle (SEP-1) is now included in the Hospital Value-Based Purchasing (VBP) Program.

Purpose: To assess the evidence supporting SEP-1 compliance or SEP-1 implementation in improving sepsis mortality.

Data sources: PubMed, Web of Science, EMBASE, CINAHL Complete, and Cochrane Library from inception to 26 November 2024.

Study selection: Studies of adults with sepsis that included 3- or 6-hour sepsis bundles defined by SEP-1 specifications.

Data extraction: Article screening, full-text review, data extraction, and risk-of-bias assessment were independently performed by 2 authors. Level of evidence was determined using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria and National Quality Forum criteria.

Data synthesis: A total of 4403 unique references were screened, and 17 studies were included. Twelve studies assessed the relationship between SEP-1 compliance and mortality; 5 showed statistically significant benefit, whereas 7 did not. Among studies showing benefit, 1 did not adjust for confounders, 1 found benefit only among patients with severe sepsis, 1 included only patients with septic shock, and 1 included only Medicare beneficiaries. Five studies assessed the relationship between SEP-1 implementation and sepsis mortality; only 1 showed significant benefit, but it did not adjust for mortality trends before SEP-1 implementation. All 17 studies were observational, and none had low risk of bias.

Limitations: The conclusions are limited by the underlying quality of the available studies, as all were observational. Because there was considerable methodologic heterogeneity among the included studies, a meta-analysis was not performed as the results could have been misleading.

Conclusion: This review found no moderate- or high-level evidence to support that compliance with or implementation of SEP-1 was associated with sepsis mortality. CMS should reconsider the addition of SEP-1 to the Hospital VBP Program.

Primary funding source: None. (PROSPERO: CRD42023482787).

Figure 1.

PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) flow diagram.

Figure 2.. Newcastle-Ottawa quality assessment for longitudinal cohort studies.

ICD-10 = International Classification of Diseases, 10th Revision; ND = no description. * Study meets quality assessment for domain category. † Included patients with ICD-10 codes for severe sepsis and septic shock with no manual validation of ICD-10 codes reported. ‡ Included only patients with sepsis-induced hypotension. § Adjusted for age and some comorbidities but not site of infection. || Included only patients with septic shock. ¶ Adjusted for age but not comorbidities or site of infection. ** Included patients with a diagnosis of sepsis at admission but did not report manual validation of diagnosis or how diagnosis was identified (e.g., ICD-10 codes). †† Included only Medicare beneficiaries. ‡‡ Included only surgical sources of sepsis. §§ Adjusted for age and site of infection but not comorbidities. |||| Measured mortality at 48 hours.

Figure 3.. Modified Newcastle-Ottawa quality assessment for before–after cohort studies.

ND = no description. * Study meets quality assessment for domain category. † Adjusted for age and comorbidities but not site of infection. ‡ Adjusted for seasonality but not preexisting trends in outcome in preimplementation period. § Sepsis was defined as patient with ≥1 blood culture who was still receiving broad-spectrum antibacterial agents 48–72 hours after blood culture collection. || Adjusted for age but not comorbidities or site of infection.

Figure 4.. Newcastle-Ottawa quality assessment for case–control studies..

SEP-1 = Severe Sepsis and Septic Shock Early Management Bundle.. * Study meets quality assessment for domain category.. † Includes patients with severe sepsis only.. ‡ Adjusted for age and some comorbidities but not site of infection.