“The timing of early antibiotics and hospital mortality in sepsis” AJRCCM, 2017, USA
Question: Does the timing of antibiotic administration in patients presenting with sepsis impact mortality?
Study Type: Retrospective study of a large healthcare database
Study Population: Adult patients presenting with sepsis (defined by ICD 9 codes + the receipt of abx within 6 hours of ED registration) to any of the 21 hospitals in the Kaiser Permanente Northern California system between 7/2010 and 12/2013.
Study Groups: Septic shock defined as need for vasopressors or initial serum lactate ³4; severe sepsis as a lactate ³2, ³1 instance of hypotension, need for invasive or non-invasive ventilation, or laboratory-determined organ dysfunction; all other patients classified as having sepsis. All vital signs obtained during the first hour were recorded and averaged. Abx administration calculated from the time of ED registration to the administration of the first abx in hours. Logistic regression was used to estimate the odds of hospital mortality based on abx timing and patient factors.
Primary Outcome: Hospital mortality
Results: 35,000 patients randomly selected. Notable patient characteristics: sepsis (35%), severe sepsis (52%), septic shock (13%), median age (73), mean first lactate (1.8), mechanical ventilation (1.4%), mortality of entire group (9.4%), mortality of patients with sepsis (3.9%), mortality of patients with severe sepsis (8.8%), mortality of patients with septic shock (26%). The fully adjusted odds ratio for hospital mortality based on abx timing was 1.09 (95% CI, 1.05-1.13) per elapsed hour after ED presentation. The absolute increase in mortality associated with a 1-hr delay in abx administration was 0.3% (95% CI, 0.01%-0.6%) for sepsis, 0.4% (95% CI, 0.1%-0.8%) for severe sepsis, and 1.8% (95% CI, 0.8%-3%) for shock.
Caveats: Retrospective, only able to describe an association not prove causation, no data provided on other aspects of early resuscitation which may impact outcome (IVF, did abx given cover causative pathogen, etc), only included patients presenting to the ED not patients who develop sepsis while hospitalized, relied upon ICD 9 codes to identify patients with sepsis.
Take-home Point: Among patients presenting to the ED with sepsis, severe sepsis, and septic shock, delays in abx administration are associated with increased mortality.
Commentary
– The most frequently cited paper on this subject is by Kumar (CCM, 2006) which retrospectively analyzed 2,731 patients with septic shock and found that for each hour delay in appropriate abx therapy after the onset of hypotension, mortality increased by 7.6%.
– The result is less dramatic here (1.8% increase for each hour delay in patients with shock) and the authors highlight several methodological differences which may account for their findings.
– The study has flaws, but it perhaps provides a more accurate look at the true mortality benefit of early abx in the modern era of sepsis management.