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. 2017 Jun 8;376(23):2235-2244.
doi: 10.1056/NEJMoa1703058. Epub 2017 May 21.

Time to Treatment and Mortality during Mandated Emergency Care for Sepsis

Christopher W Seymour  1 , Foster Gesten  1 , Hallie C Prescott  1 , Marcus E Friedrich  1 , Theodore J Iwashyna  1 , Gary S Phillips  1 , Stanley Lemeshow  1 , Tiffany Osborn  1 , Kathleen M Terry  1 , Mitchell M Levy  1
Affiliations

Time to Treatment and Mortality during Mandated Emergency Care for Sepsis

Christopher W Seymour et al. N Engl J Med. .

Abstract

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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Figures

Figure 1
Figure 1. Cumulative Probability of Completion of the 3-Hour Bundle, Administration of Broad-Spectrum Antibiotics, and Completion of the Initial Intravenous-Fluid Bolus after the Time That the Sepsis Protocol Was Initiated
The 3-hour bundle for the care of patients with sepsis or septic shock had to include receipt of the following care within 3 hours: obtaining of a blood culture before the administration of antibiotics, measurement of the serum lactate level, and the administration of broad-spectrum antibiotics; however, protocols could be tailored by each hospital. We also assessed the time to the administration of broad-spectrum antibiotics and the time to the completion of an initial bolus of intravenous fluids.
Figure 2
Figure 2. Risk-Adjusted Odds Ratios of In-Hospital Death in the Primary Model and Prespecified Subgroups
Shown are odds ratios, with 95% confidence intervals, for in-hospital death for each hour that it took to complete the 3-hour bundle. Other site of infection includes gastrointestinal, skin, central nervous system, and unknown.
Figure 3
Figure 3. Crude In-Hospital Mortality and Predicted Risks of In-Hospital Death
Shown are the crude in-hospital mortality and predicted risks of in-hospital death, with adjustment for covariates across a range of time after protocol initiation, for the completion of the 3-hour bundle of sepsis care (Panel A), the administration of broad-spectrum antibiotics (Panel B), and the completion of the initial bolus of intravenous fluids (Panel C) in a typical patient. I bars represent 95% confidence intervals.
Figure 4
Figure 4. Reliability-Adjusted Rate for Each Hospital for Completion of the 3-Hour Bundle in 3 Hours, According to Hospital Rank
The 149 hospitals that were included in the study were ranked from lowest to highest, with higher numbers indicating a greater likelihood of completing the 3-hour bundle within 3 hours. I bars represent 95% confidence intervals.
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