Duration of hypotension before initiation of effective antimicrobial therapy in septic shock
Kumar 2006 trial design and results
Design
Retrospective multicentre cohort study
Treatment
Effective antimicrobial therapy given earlier after the onset of hypotension
Control
Later administration
Population
2731 adult patients with septic shock across 14 intensive care units
Follow-up
Hospital discharge
Primary endpoint
Survival to hospital discharge
Result
Among the 2154 patients (78.9%) who received effective antimicrobial therapy only after the onset of hypotension, each hour of delay carried an adjusted odds ratio for in-hospital death of 1.119 (95% CI 1.103 to 1.136, p<0.0001). Administration within the first hour of documented hypotension was associated with the highest survival to discharge.
Secondary endpoints
Mortality by hour of delay
Effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock.
The trial authors, in the published abstract
How it has aged
The single most influential observational study in sepsis, and the origin of the one-hour antibiotic target embedded in quality metrics worldwide. It is retrospective, and sicker patients are both harder to treat promptly and more likely to die — confounding that no randomised trial has been able to resolve, because no one will randomise delay.
Publications
Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock
Kumar A, Roberts D, Wood KE, 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 Jun;34(6):1589-96.
Survival highest when effective antibiotics given within the first hour of hypotension
Progressive rise in mortality with each hour of delay
Retrospective design, vulnerable to confounding by severity