The Surviving Sepsis Campaign guidelines recommend initiating broad-spectrum antibiotics within one hour to treat severe sepsis or septic shock. In September’s Critical Care Medicine, Puskarich et al studied the association between time to initial antibiotic administration and in-hospital mortality rates for septic patients treated with the quantitative resuscitation protocol. The study design was a preplanned analysis of a recently completed multicenter prospective, parallel-group, non-blinded randomized clinical trial. The authors hypothesized that timing of antibiotic administration was associated with the primary outcome of in-hospital mortality rates.

Consecutive patients with confirmed or suspected infection, and two or more systemic inflammatory response syndrome criteria, were enrolled. Of the 291 patients assigned to one of two quantitative resuscitation protocols, the median time from triage to initial antibiotic administration was 115 minutes (interquartile range, 65-175).  A multivariate logistic regression model did not reveal any evidence for confounding since adjusted odds ratios were not significantly different from unadjusted odds ratios when multiple independent variables were evaluated. No association was found between in-hospital mortality rates when antibiotics were given within six hours of initial triage in the emergency department (ED). However, patients who received antibiotics after recognition of shock (n = 172) had a higher mortality rate (n = 119, odds ratio 2.35; 95% CI, 1.12-4.53).

The recommendation for administering antibiotics within one hour for severe sepsis and septic shock is based on expert opinion and a previous large retrospective study that demonstrated higher survival rates when antibiotics were given within one hour. In this most recent study, investigators were unable to show increased mortality rates for each hour’s delay to administration of antibiotics after emergency department triage; although, when antibiotics were delayed for patients in shock, mortality rates increased. These findings, which showed no difference in mortality rates when antibiotics were delayed after triage (but not shock), may be partly attributed to a relatively small sample size, the fact that each participating institution had robust resuscitation protocols, and a lower overall mortality rate for septic shock than described in previous studies. The findings in this study may also be credited to the effect of an early goal-directed resuscitation protocol, in which antibiotics are one of several crucial elements of current evidence-based support for patients with severe sepsis and septic shock.
Jing Tao, MD, senior resident in the Department of Anesthesiology at the University of Maryland, contributed to this installment of Concise Critical Appraisal.

Concise Critical Appraisal is a regular feature authored by SCCM member Samuel M. Galvagno Jr., DO. Each installment highlights journal articles most relevant to the critical care practitioner.

  1. Dellinger RP, et al.  Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008.  Crit Care Med 2008; 36: 296-327.
  2. Jones AE, et al.  Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: A randomized clinical trial.  JAMA 2010; 303: 739-746.
  3. Kumar A, et al.  Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.  Crit Care Med 2006; 34: 1589-1596.