This article has been corrected. To see what has changed, please read the Letter to the Editor and the authors' response. The original version (PDF) is appended to this article as a Supplement.
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).
The treatment of severe sepsis involves multiple interventions each of which has a variable amount of evidence to support its use. The Severe Sepsis and Septic Shock Early Management Bundle includes 7 specific interventions that are bundled together as a package and called "Sep-1". The use or non-use of the bundle as a whole became the basis for judging adequacy of practice, an element of hospital accreditation, and used as a pay for performance measure to adjust reimbursement to hospitals. The authors reviewed the evidence for the individual components of the bundle and found that the 5 hemodynamic interventions included in the bundle do not have robust evidence to support their use. Both the understanding of what constitutes evidence-in-practice and how this is unproblematically transmuted into evidence to support 'policy' remains simplistic and naive, particularly for use in complex interventions. This paper illustrates this phenomenon.
It's unfortunate that there is no moderate or high quality evidence. This report therefore leaves us uncertain.
The sepsis management bundles have been promoted beyond the evidence that supports them. These bundles may have no effect, or may be harmful, and are certainly expensive. Medical practice should be based on evidence rather than administrative foible.