Dominique J. Pepper, MBChB, MD; Dharmvir Jaswal, MD; Junfeng Sun, PhD; Judith Welsh, BSN, MLS; Charles Natanson, MD; Peter Q. Eichacker, MD
Disclaimer: The opinions expressed in this manuscript belong to the authors and do not represent the National Institutes of Health or any other division of the U.S. Department of Health and Human Services. Drs. Pepper and Eichacker had full access to all study data and take responsibility for the integrity of the data and accuracy of the analysis.
Financial Support: By intramural funding from the National Institutes of Health.
Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-2947.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: PROSPERO CRD42016052716 and in the Supplement (available at Annals.org). Statistical code: Not applicable. Data set: See tables, figures, and Supplement. Additional data are available from Dr. Eichacker (e-mail, firstname.lastname@example.org).
Requests for Single Reprints: Peter Q. Eichacker, MD, Critical Care Medicine Department, National Institutes of Health, Building 10, Room 2C145, Bethesda, MD 20892; e-mail, email@example.com.
Current Author Addresses: Drs. Pepper, Jaswal, Sun, Natanson, and Eichacker and Ms. Welsh: National Institutes of Health, 10 Center Drive, Bethesda, MD 20892.
Author Contributions: Conception and design: D.J. Pepper, J. Welsh, C. Natanson, P.Q. Eichacker.
Analysis and interpretation of the data: D.J. Pepper, J. Sun, C. Natanson, P.Q. Eichacker.
Drafting of the article: D.J. Pepper, J. Sun, J. Welsh, C. Natanson, P.Q. Eichacker.
Critical revision of the article for important intellectual content: D.J. Pepper, J. Sun, C. Natanson, P.Q. Eichacker.
Final approval of the article: D.J. Pepper, D. Jaswal, J. Sun, J. Welsh, C. Natanson, P.Q. Eichacker.
Statistical expertise: J. Sun, C. Natanson.
Obtaining of funding: P.Q. Eichacker.
Collection and assembly of data: D.J. Pepper, D. Jaswal, P.Q. Eichacker.
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.
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.
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.
PubMed, Embase, Scopus, Web of Science, and ClinicalTrials.gov from inception to 28 November 2017 with no language restrictions.
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.
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.
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.
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.
No high- or moderate-level evidence shows that SEP-1 or its hemodynamic interventions improve survival in adults with sepsis.
National Institutes of Health. (PROSPERO: CRD42016052716)
Pepper DJ, Jaswal D, Sun J, Welsh J, Natanson C, Eichacker PQ. Evidence Underpinning the Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Management Bundle (SEP-1): A Systematic Review*. Ann Intern Med. [Epub ahead of print 20 February 2018]:. doi: 10.7326/M17-2947
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Published: Ann Intern Med. 2018.
Healthcare Delivery and Policy, Multi-Organ Failure and Sepsis, Pulmonary/Critical Care.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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