By Vibhu Sharma, MD, MS

Associate Professor of Medicine, University of Colorado, Denver

SYNOPSIS: A longitudinal study of a single health system’s adherence to and outcomes of Medicare Sepsis Performance Measures (SEP-1) did not show an improvement in mortality despite improvements in adherence to guideline-mandated care.

SOURCE: Barbash IJ, Davis BS, Yabes JG, et al. Treatment patterns and clinical outcomes after the introduction of the Medicare Sepsis Performance Measure (SEP-1). Ann Intern Med 2021;174:927-935.

The Centers for Medicare and Medicaid Services (CMS) began requiring hospitals to report data on compliance to the Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) beginning in October 2015. This longitudinal study reports the effect of all-or-none adherence to the SEP-1 bundle within 11 hospitals comprising the University of Pittsburgh health system over a period of two years (2015-2017). SEP-1 has three- and six-hour bundles. The components of the three-hour bundle in patients with suspected sepsis include blood cultures drawn prior to antibiotic administration, antibiotic administration within three hours of sepsis identification, and baseline blood lactate levels. Additionally, if septic shock is identified at “time zero,” administration of a 30 mL/kg bolus of crystalloid is included in the three-hour bundle. The six-hour bundle includes a recheck of lactate if initially elevated, a repeat assessment of tissue perfusion and volume status if treated for septic shock, and vasopressors for refractory hypotension (systolic blood pressure < 90 mmHg despite fluid resuscitation).

In this study, Barbash et al used electronic health record (EHR)-level data for adults hospitalized with community-onset sepsis, with time zero defined as the time that the first order for a body fluid culture was placed. Results of 54,225 encounters for adult patients with sepsis admitted through the emergency department were reported, approximately half of whom represent patient encounters prior to SEP-1 bundle implementation. From the EHR, the authors extracted the use of process measures in the SEP-1 bundle pre-implementation (Q3 of 2015, prior to system-wide implementation) and used these measures to predict use of SEP-1 bundle measures in Q4 of 2017 if SEP-1 criteria had not been implemented. The statistical model that was generated assumed that if SEP-1 criteria had not been implemented, trends in intensive care unit (ICU) admission and mortality would have remained unchanged over the period from 2015 to 2017. Actual utilization of bundle measures in Q4 of 2017 then was compared to predicted utilization of measures in Q4 2017 if SEP-1 criteria had not been implemented.

Patient characteristics before and after bundle implementation were similar. This included demographic characteristics as well as severity of illness scores. There were variable changes in the adoption of measures. Rates of lactate measurement within three hours, 30 mL/kg crystalloid boluses, and antibiotic administration within three hours increased; use of vasopressors was unchanged. There were no meaningful (or statistically significant) changes in rates of admission to the ICU or mortality after implementation of SEP-1, even in a subgroup analysis of patients with septic shock. However, the authors did note the wide confidence intervals in terms of mortality and, as such, could not exclude the possibility of an important clinical effect.


Although adherence to individual components of a sepsis management bundle may have an impact on outcomes,1 an all-or-none adherence to SEP-1 criteria has not been consistently shown to improve outcomes for either community-onset sepsis2,3 or hospital-onset sepsis.4

On the other hand, implementation of SEP-1-mandated measures may increase the prescription of unnecessarily broad-spectrum antibiotic therapy.5 The Infectious Diseases Society of America (IDSA) has expressed concern about the potential for SEP-1 criteria to drive unnecessary antibiotic use due to overdiagnosis of sepsis as well as the mandate for antibiotic therapy for suspected sepsis.6 This mostly is related to determination of when the clock begins for the three-hour and six-hour implementation windows. The authors of the IDSA position paper noted that a “time zero” definition of sepsis is not evidence-based and can vary widely depending on the provider.6

A meta-analysis of 17 observational studies assessed the impact of fluid and antibiotic bundles.7 All the included studies had a high risk of bias. Although bundles were associated with increased odds of survival, there was substantial heterogeneity of studies in this meta-analysis. The pooled analysis failed to demonstrate superiority of specifically timed antibiotic administration or a specific volume of fluid. Fluid therapy in sepsis is not without risk, as demonstrated by the landmark FEAST trial.8 Excess mortality due to cardiovascular collapse was found among children with septic shock who received a 20-40 mL/kg fluid bolus compared to those who were randomized to no bolus.

Over-reliance on protocols in the management of sepsis may lead to missed diagnoses. Clinicians may develop inertia with respect to patients presenting with sepsis, deferring to an all-or-none protocol and “boxes to be checked” approach, especially in busy emergency departments. Critically ill patients with sepsis deserve a careful assessment of physiology. Examples from clinical practice of patients who could worsen despite tight adherence to SEP-1 guidelines include those with unrecognized cardiogenic shock, severe aortic stenosis, left ventricular outflow tract obstruction related to systolic anterior motion of the anterior mitral leaflet, pulmonary embolism, adrenal insufficiency, abdominal compartment syndrome, and right ventricular failure. No benefit is expected, and harm may result in these scenarios with SEP-1-mandated fluid therapy. In all these scenarios, an increasing lactate indicates worsening tissue perfusion but not worsening sepsis. Given the overall low quality of evidence informing the utility of SEP-1 criteria, good-quality, individualized care remains the cornerstone of management of patients with sepsis and septic shock.


  1. Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017;376:2235-2244.
  2. Barbash IJ, Davis B, Kahn JM. National performance on the Medicare SEP-1 sepsis quality measure. Crit Care Med 2019;47:1026-1032.
  3. Rhee C, Filbin MR, Massaro AF, et al. Compliance with the national SEP-1 quality measure and association with sepsis outcomes: A multicenter retrospective cohort study. Crit Care Med 2018;46:1585-1591.
  4. Baghdadi JD, Brook RH, Uslan DZ, et al. Association of a care bundle for early sepsis management with mortality among patients with hospital-onset or community-onset sepsis. JAMA Intern Med 2020;180:707-716.
  5. Miller J, Hall B, Wilson K, Cobian J. Impact of SEP-1 on broad-spectrum combination antibiotic therapy in the emergency department. Am J Emerg Med 2020;38:2570-2573.
  6. Rhee C, Chiotos K, Cosgrove SE, et al. Infectious Diseases Society of America position paper: Recommended revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) sepsis quality measure. Clin Infect Dis 2021;72:541-552.
  7. Pepper DJ, Sun J, Cui X, et al. Antibiotic- and fluid-focused bundles potentially improve sepsis management, but high-quality evidence is lacking for the specificity required in the Centers for Medicare and Medicaid Service’s Sepsis Bundle (SEP-1). Crit Care Med 2019;47:1290-1300.
  8. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011;364:2483-2495.