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Survival Benefit and Cost Savings From Compliance With a Simplified 3-Hour Sepsis Bundle in a Series of Prospective, Multisite, Observational Cohorts

Leisman, Daniel E. BS1,2; Doerfler, Martin E. MD3; Ward, Mary Frances RN, MS, ANP4,5; Masick, Kevin D. PhD6; Wie, Benjamin J. BA1; Gribben, Jeanie L. BS1; Hamilton, Eric BA6; Klein, Zachary MS6; Bianculli, Andrea R. BS1; Akerman, Meredith B. MS5; D’Angelo, John K. MD1; D’Amore, Jason A. MD1

doi: 10.1097/CCM.0000000000002184
Feature Articles

Objectives: To determine mortality and costs associated with adherence to an aggressive, 3-hour sepsis bundle versus noncompliance with greater than or equal to one bundle element for severe sepsis and septic shock patients.

Design: Prospective, multisite, observational study following three sequential, independent cohorts, from a single U.S. health system, through their hospitalization.

Setting: Cohort 1: five tertiary and six community hospitals. Cohort 2: single tertiary, academic medical center. Cohort 3: five tertiary and four community hospitals.

Patients: Consecutive sample of all severe sepsis and septic shock patients (defined: infection, ≥ 2 systemic inflammatory response syndrome, and hypoperfusive organ dysfunction) identified by a quality initiative. The exposure was full 3-hour bundle compliance. Bundle elements are as follows: 1) blood cultures before antibiotics; 2) parenteral antibiotics administered less than or equal to 180 minutes from greater than or equal to two systemic inflammatory response syndrome “and” lactate ordered, or less than or equal to 60 minutes from “time-zero,” whichever occurs earlier; 3) lactate result available less than or equal to 90 minutes postorder; and 4) 30 mL/kg IV crystalloid bolus initiated less than or equal to 30 minutes from “time-zero.” Main outcomes were in-hospital mortality (all cohorts) and total direct costs (cohorts 2 and 3).

Measurements and Main Results: Cohort 1: 5,819 total patients; 1,050 (18.0%) bundle compliant. Mortality: 604 (22.6%) versus 834 (26.5%); CI, 0.9–7.1%; adjusted odds ratio, 0.72; CI, 0.61–0.86; p value is less than 0.001. Cohort 2: 1,697 total patients; 739 (43.5%) bundle compliant. Mortality: 99 (13.4%) versus 171 (17.8%), CI, 1.0–7.9%; adjusted odds ratio, 0.60; CI, 0.44–0.80; p value is equal to 0.001. Mean costs: $14,845 versus $20,056; CI, –$4,798 to –5,624; adjusted β, –$2,851; CI, –$4,880 to –822; p value is equal to 0.006. Cohort 3: 7,239 total patients; 2,115 (29.2%) bundle compliant. Mortality: 383 (18.1%) versus 1,078 (21.0%); CI, 0.9–4.9%; adjusted odds ratio, 0.84; CI, 0.73–0.96; p value is equal to 0.013. Mean costs: $17,885 versus $22,108; CI, –$2,783 to –5,663; adjusted β, –$1,423; CI, –$2,574 to –272; p value is equal to 0.015.

Conclusions: In three independent cohorts, 3-hour bundle compliance was associated with improved survival and cost savings.

1Department of Emergency Medicine, Hofstra-Northwell School of Medicine, Hempstead, NY.

2Icahn School of Medicine at Mount Sinai, New York, NY.

3Department of Medicine, Hofstra-Northwell School of Medicine, Hempstead, NY.

4Department of Neurosurgery, Hofstra-Northwell School of Medicine, Hempstead, NY.

5Feinstein Institute for Medical Research, Manhasset, NY.

6Krasnoff Quality Management Institute, Northwell Health System, New Hyde Park, NY.

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Supported, in part, by a grant from the Center for Medicare and Medicaid Innovation (CMMI) to the High Value Healthcare Collaborative, of which the study sites’ parent health system (Northwell Health) was a part. This grant helped funding the underlying quality improvement program and database in this study but did not directly fund research activity or investigators.

Dr. Doerfler disclosed other support (ongoing employment) and received funding from Northwell Health (employer). Ms. Ward was a site subinvestigator for the National Institutes of Health funded Process Clinical Trial. Ms. Ward and Dr. D'Amore disclosed government work, and received support for article research from CMMI. Their institution received funding from CMMI subcontract grant with Dartmouth College. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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