BOSTON – Delaying antibiotics until after onset of septic shock was associated with increased mortality in a prospective study of 300 patients who presented to the emergency department with suspected infection and were treated with a quantitative resuscitation protocol.
However, there was no increase in mortality with hourly delays in antibiotics after shock onset up to 3 hours, said Dr. Michael A. Puskarich of the Carolinas Medical Center, Charlotte, N.C.
"When we gave antibiotics before the recognition of shock, patients did better. One of the limitations of that, however, it’s really impossible to predict when you’re seeing the patient when there will be shock recognition. Therefore, our recommendation is still to give broad-spectrum antibiotics as early as possible while not sacrificing hemodynamic resuscitation. However, also based on these data, we cannot support a specific time frame from triage or from shock recognition to suggest a time-to-antibiotic-dose core measure for septic shock at this point," Dr. Puskarich said in an interview.
International guidelines call for administration of broad-spectrum antibiotic therapy within 1 hour of diagnosis of septic shock and severe sepsis without septic shock, as part of a quantitative resuscitation protocol (Crit. Care Med. 2008;36:296-327). These guidelines were based largely on one study that found that effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality with increasing delays, only 50% of septic shock patients received effective antimicrobial therapy within 6 hours of documented hypotension (Crit. Care Med. 2006;34:1589-96).
The current study was a preplanned secondary analysis of a previously published study designed to test the hypothesis of noninferiority between lactate clearance and central venous oxygen saturation (ScvO2) as goals of early sepsis resuscitation (JAMA 2010;303:739-46). Patients were enrolled from three large, urban, tertiary care emergency departments. Inclusion criteria were suspected infection with two or more systemic inflammatory response syndrome criteria.
All patients received structure resuscitation with targets of central venous pressure 8 mm Hg or greater, a mean arterial pressure 65 mm Hg or greater, and either ScvO2 greater than or equal to 70% or lactate clearance greater than or equal to 10%. Broad-spectrum antibiotics were given according to local institution guidelines, as early as practical in the course of the resuscitation, Dr. Puskarich said at the annual meeting of the Society for Academic Emergency Medicine.
Of the 300 patients who had been randomized to either the lactate or ScvO2 target groups, 9 had received antibiotics prior to arrival and were excluded. Of the remaining 291 patients, 59% (172) received the initial dose of antibiotics after shock onset. Median time from triage to shock recognition was 89 minutes. The patients had a mean age of 62 years, 54% were white, and 53% were male. Median systolic blood pressure was 86 mm Hg, and median venous lactate was 3.3 mmol/L. The median ED sepsis-related organ failure assessment score was 6.
Overall mortality was 55%, and the majority of survivors and nonsurvivors received antibiotics within the same time frame. Patients who received antibiotics after shock recognition were more than twice as likely to die as were those who received them prior to shock recognition, 24% vs. 12%, with an unadjusted odds ratio of 2.3 that remained significant after adjustment for confounders. However, there was no increase in mortality by hourly delays from either triage or shock onset up to 3 hours, Dr. Puskarich reported.
"When early sepsis hemodynamic resuscitation is sufficiently refined, the strength of the association between hourly delays in antibiotic administration and mortality appears to recede. The effect of timing in the most proximal phase of septic shock remains unclear," he concluded.
Dr. Puskarich received grant support from the American Heart Association. The study for which this was a secondary analysis was funded by the National Institutes of Health. He said he had no other relevant financial disclosures.