Evidence Underpinning the Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Management Bundle (SEP-1): A Systematic Review

Abstract

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Background: The Severe Sepsis and Septic Shock Early Management Bundle (SEP-1), the sepsis performance measure introduced in 2015 by the Centers for Medicare & Medicaid Services (CMS), requires the reporting of up to 5 hemodynamic interventions, as many as 141 tasks, and 3 hours to document for a single patient.

Purpose: To evaluate whether moderate- or high-level evidence shows that use of the 2015 SEP-1 or its hemodynamic interventions improves survival in adults with sepsis.

Data sources: PubMed, Embase, Scopus, Web of Science, and ClinicalTrials.gov from inception to 28 November 2017 with no language restrictions.

Study selection: Randomized and observational studies of death among adults with sepsis who received versus those who did not receive either the entire SEP-1 bundle or 1 or more SEP-1 hemodynamic interventions, including serial lactate measurements; a fluid infusion of 30 mL/kg of body weight; and assessment of volume status and tissue perfusion with a focused examination, bedside cardiovascular ultrasonography, or fluid responsiveness testing.

Data extraction: Two investigators independently extracted study data and assessed each study's risk of bias; 4 authors rated level of evidence by consensus using CMS criteria published in 2013. High- or moderate-level evidence required studies to have no confounders and low risk of bias.

Data synthesis: Of 56 563 references, 20 studies (18 reports) met inclusion criteria. One single-center observational study reported lower in-hospital mortality after implementation of the SEP-1 bundle. Sixteen studies (2 randomized and 14 observational) reported increased survival with serial lactate measurements or 30-mL/kg fluid infusions. None of the 17 studies were free of confounders or at low risk of bias. In 3 randomized trials, fluid responsiveness testing did not alter survival.

Limitations: Few trials, poor-quality and confounded studies, and no studies (with survival outcomes) of the focused examination or bedside cardiovascular ultrasonography. Use of the 2015 version of SEP-1 and 2013 version of CMS evidence criteria, both of which were updated in 2017.

Conclusion: No high- or moderate-level evidence shows that SEP-1 or its hemodynamic interventions improve survival in adults with sepsis.

Primary funding source: National Institutes of Health. (PROSPERO: CRD42016052716).

Appendix Figure.

Evidence search and selection. SEP-1 = Severe Sepsis and Septic Shock Early Management Bundle. * 1 of these investigated 3 individual cohorts of patients, and each cohort is treated as a separate study in this analysis. Twenty total studies were analyzed.

Figure 1.

Summary of the proportion of patients receiving early antibiotics or the time to antibiotic administration among serial lactate and 30-mL/kg fluid infusion sepsis studies. Ten of the 16 studies examining serial lactate measurements, a 30-mL/kg fluid infusion, or both provided data showing that a greater proportion of intervention than control patients received appropriate early antibiotics (6 studies) or that the time to antibiotic administration was shorter in intervention than control patients (7 studies). * Antibiotic data were not reported. † Only a point estimate with no 95% CIs for time to antibiotics was provided. ‡ Leisman and colleagues (31) analyzed 3 cohorts of patients representing 3 individual studies. This year indicates the final year of the cohort’s enrollment. § Intervention groups were treated with early antibiotics, but no data were provided.

Figure 2.

Summary of survival, confounders, and risk of bias among serial lactate and 30-mL/kg fluid infusion sepsis studies. Although the 16 studies testing serial lactate measurements, a 30-mL/kg fluid infusion, or both reported increased survival (odds ratio of survival and 95% CI) in intervention compared with control patients, they all included confounders related to earlier antibiotic administration or adjunctive aid use in intervention patients or had incomplete intervention data. All 16 studies were at high or unknown risk of bias. A dash indicates that the study did not investigate the intervention and therefore data could not be reported. The × indicates that the study reported the actual volume of fluid administered. * Leisman and colleagues (31) analyzed 3 cohorts of patients representing 3 individual studies. This year indicates the final year of the cohort’s enrollment.