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Time to treatment and mortality during mandated emergency care for sepsis.
Open accessAbstract
BACKGROUND: In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. METHODS: We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. RESULTS: Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). CONCLUSIONS: More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).
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In the citing paper
“Implementing standardized bundles can help ensure timely and proper sepsis care and has been associated with reductions in mortality [11-13].”
From Integrating a Machine Learning System Into Clinical Workflows: Qualitative Study (2020) · cites this paper as [13]
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In the citing paper
“The observed reductions in ICU length of stay (1.8 days), mechanical ventilation duration (2.3 days), and 28-day mortality (5.7%) are clinically meaningful and compare favorably with other sepsis intervention studies22,23.”
From Machine learning predicts sepsis deterioration trajectories. (2026) · cites this paper as [22]
Experimental — accuracy not yet measuredIn the citing paper
“In a study of 49,331 patients treated at 149 New York hospitals, each additional hour of time from ED arrival to administration of antimicrobials was associated with 1.04 increased odds of in-hospital mortality, p < 0.001 (1.07 (95% CI 1.05–1.09) for patients receiving vasopressors vs. 1.01 (95% CI 0.99–1.04) for patients not on vasopressors) [98].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [98]
In the citing paper
“In patients with sepsis without shock, the association between time to antimicrobials and mortality within the first few hours from presentation is less consistent [98, 110].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [98]
In the citing paper
“The mortality reduction associated with early antimicrobials appears strongest in patients with septic shock, where a number of studies have reported a strong association between time-to-antibiotics and death in patients with septic shock but weaker associations in patients without septic shock [98, 109, 110].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [98]
In the citing paper
“Observational studies do, however, suggest that mortality may increase after intervals exceeding 3–5 h from hospital arrival and/or sepsis recognition [98, 111, 119, 120].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [98]
In the citing paper
“Early administration of appropriate antimicrobials is one of the most effective interventions to reduce mortality in patients with sepsis [96–98].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [98]
In the citing paper
“Early administration of appropriate antimicrobial therapy can be life-saving in patients with sepsis”
From Trends in empiric broad-Spectrum antibiotic use for suspected community-onset Sepsis in US hospitals (2024) · cites this paper as [1]
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Loots, F. J., Smits, M., Hopstaken, R., Jenniskens, K., Schroeten, F. H., den Bruel, A. V., van de Pol, A. C., Oosterheert, J. J., Bouma, H. R., Little, P. S., et al. (2022) · British Journal of General Practice · doi:10.3399/bjgp.2021.0520 · Cited by 10
Early Diuretics for De-resuscitation in Septic Patients With Left Ventricular Dysfunction
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Al-Kader, D. A., Anwar, S., Hussaini, H., Amaowei, E. E. J., Rasuli, S. F., Hussain, N., Kaddo, S., & Memon, A. (2022) · Cureus · doi:10.7759/cureus.32405 · Cited by 11
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Metadata
- Authors
- Seymour, C. W., Gesten, F., Prescott, H. C., Friedrich, M. E., Iwashyna, T. J., Phillips, G. S., Lemeshow, S., Osborn, T., Terry, K. M., & Levy, M. M.
- Affiliations
- New York State Department of Health (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-06-08
- Volume
- 376
- Issue
- 23
- Pages
- 2235-2244
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC5538258
- OpenAlex
- W2614741637
- Semantic Scholar
- 62b9aa37782c55c987f30172befdf1a32ae2a027
- Cited by
- 2,225
- References
- 26
- Citations by year
- 2026: 254 · 2025: 215 · 2024: 245 · 2023: 266 · 2022: 279 · 2021: 241 · 2020: 267 · 2019: 233 · 2018: 176 · 2017: 46
- FWCI
- 154.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Health Services Research and Development (13-079, 11-109)
- National Institutes of Health
- National Cancer Institute (P30CA016058)
- National Institute of General Medical Sciences (K08GM115859, R35GM119519)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Abdominal Surgery and Complications
- Health Sciences › Medicine › Emergency Medicine › Emergency and Acute Care Studies
- Keywords
- sepsis, septic shock, time to treatment, sepsis protocol, antibiotic administration, fluid bolus, in-hospital mortality, emergency department care, risk-adjusted mortality, blood culture, lactate measurement, broad-spectrum antibiotics
- MeSH terms
- Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents, Combined Modality Therapy, Emergency Treatment, Female, Fluid Therapy, Humans, Infusions, Intravenous, Male, Middle Aged, Retrospective Studies, Shock, Septic, Multivariate Analysis, Hospital Mortality, Sepsis, Clinical Audit, Time-to-Treatment
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