Does SEP-1 increase sepsis mortality?

Implementation of or compliance with the Severe Sepsis and Septic Shock Management Bundle (SEP-1) does not appear to contribute to mortality among patients with sepsis, as shown by the results of a systematic review.

The databases of PubMed, Web of Science, Embase, Cinahl Complete, and Cochrane Library were searched from inception to 26 November 2024 for studies of adults with sepsis that included 3- or 6-h sepsis bundles defined by SEP-1 specifications.

Two authors independently performed article screening, full-text review, data extraction, and risk-of-bias assessment. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and National Quality Forum criteria were used to assess the level of evidence.

In total, 4,403 unique references were identified, of which 17 met the eligibility criteria. Twelve studies explored the association between SEP-1 compliance and mortality, with five showing statistically significant benefit and seven that did not.

One of the five studies that showed benefit did not adjust for confounders, while one reported benefit only among patients with severe sepsis, one included only patients with septic shock, and another included only Medicare beneficiaries.

Five studies examined the link between SEP-1 implementation and sepsis mortality, but only one found a significant benefit. However, this study did not adjust for mortality trends before SEP-1 implementation.

Of note, all 17 studies were observation in design, none of which had a low risk of bias.

“The Centers for Medicare and Medicaid Services should reconsider the addition of SEP-1 to the Hospital Value-Based Purchasing Program,” the authors said. 

This systematic review was limited by the underlying quality of the available studies, as all were observational. In addition, a meta-analysis was not carried out because the results could have been misleading due to the considerable methodological heterogeneity among the included studies.