title: Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol.
abstract: 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.
  
  
  METHODS
  Preplanned analysis of a multicenter randomized controlled trial of early sepsis resuscitation.
  
  
  METHODS
  Three urban U.S. emergency departments.
  
  
  METHODS
  Adult patients with septic shock.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Puskarich
authors.forename: Stephen
authors.initials: S
authors.lastname: Trzeciak
authors.forename: Nathan I
authors.initials: NI
authors.lastname: Shapiro
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Arnold
authors.forename: James M
authors.initials: JM
authors.lastname: Horton
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Studnek
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kline
authors.forename: Alan E
authors.initials: AE
authors.lastname: Jones
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology; D002496:Central Venous Pressure / Q000502:physiology; D002985:Clinical Protocols; D004636:Emergency Service, Hospital; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007773:Lactates / Q000097:blood; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D012151:Resuscitation / Q000379:methods*; D012772:Shock, Septic / Q000401:mortality* / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D007773:Lactates; D010100:Oxygen