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Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol*

Puskarich, Michael A. MD; Trzeciak, Stephen MD; Shapiro, Nathan I. MD; Arnold, Ryan C. MD; Horton, James M. MD; Studnek, Jonathan R. PhD; Kline, Jeffrey A. MD; Jones, Alan E. MD on behalf of the Emergency Medicine Shock Research Network (EMSHOCKNET)

doi: 10.1097/CCM.0b013e31821e87ab
Clinical Investigations

Objective: We sought to determine the association between time to initial antibiotics and mortality of patients with septic shock treated with an emergency department-based early resuscitation protocol.

Design: Preplanned analysis of a multicenter randomized controlled trial of early sepsis resuscitation.

Setting: Three urban U.S. emergency departments.

Patients: Adult patients with septic shock.

Interventions: A quantitative resuscitation protocol in the emergency department targeting three physiological variables: central venous pressure, mean arterial pressure, and either central venous oxygen saturation or lactate clearance. The study protocol was continued until all end points were achieved or a maximum of 6 hrs.

Measurements and Main Results: Data on patients who received an initial dose of antibiotics after presentation to the emergency department were categorized based on both time from triage and time from shock recognition to initiation of antibiotics. The primary outcome was inhospital mortality. Of 291 included patients, mortality did not change with hourly delays in antibiotic administration up to 6 hrs after triage: 1 hr (odds ratio [OR], 1.2; 0.6–2.5), 2 hrs (OR, 0.71; 0.4–1.3), 3 hrs (OR, 0.59; 0.3–1.3). Mortality was significantly increased in patients who received initial antibiotics after shock recognition (n = 172 [59%]) compared with before shock recognition (OR, 2.4; 1.1–4.5); however, among patients who received antibiotics after shock recognition, mortality did not change with hourly delays in antibiotic administration.

Conclusion: In this large, prospective study of emergency department patients with septic shock, we found no increase in mortality with each hour delay to administration of antibiotics after triage. However, delay in antibiotics until after shock recognition was associated with increased mortality.

From the Departments of Emergency Medicine (MAP, JRS, JAK, AEJ) and Medicine (JMH), Carolinas Medical Center, Charlotte, NC; the Departments of Medicine, Division of Critical Care Medicine (ST), and Emergency Medicine (ST, RCA), Cooper University Hospital, Camden, NJ; and the Department of Emergency Medicine and Center for Vascular Biology Research (NIS), Beth Israel Deaconess Medical Center, Boston, MA.

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Dr. Jones is now affiliated with the University of Mississippi School of Medicine, Jackson, MS.

This work was supported by grant K23GM076652 (A.E.J.) from the National Institute of General Medical Sciences/National Institutes of Health. Dr. Puskarich is supported by grant 10POST3560001 from the American Heart Association. Dr. Trzeciak is supported by grant GM083211 from the National Institute of General Medical Sciences/National Institutes of Health. Dr. Shapiro was supported by grants HL091757 and GM076659 from the National Institutes of Health. Dr. Horton has participated in HIV trials with Gilead and GlaxoSmithKline and has received support from the Cannon and Silverman Foundations. Dr. Kline holds stock ownership in CP Diagnostics and received US patents. The remaining authors have not disclosed any potential conflicts of interest.

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© 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins