Fig. 1
Crude outcomes and predicted outcomes depending on time to treatment. Presented are the risk (bars) and predicted risk (lines) across a range of time after onset of sepsis. Bold lines present the predicted risk with 95% confidence interval for a typical patient from a model adjusting for covariates, dotted lines present the predicted risk with 95% confidence interval from a model without adjusting for covariates. The effect of timing was tested for linearity by fractional polynomials at significance level 0.05; in panels a to c timing is treated as linear, since no significant deviation from linearity was found. Models adjusted for the following covariates: age and gender, origin of infection, location of the patient at the onset of sepsis, focus of infection, microbiological confirmation of infection, study phase (trial vs. surveillance phase), and group the hospital was randomized to (intervention vs. control). a Effect of time to antimicrobial therapy within the first 48 h on 28-day mortality. N = 4792 cases were treated with antimicrobials within 48 h after sepsis onset, of which 4659 (97%) cases had complete data on outcome and covariates for analysis. b Effect of timing of surgical source control within the first 48 h on 28-day mortality. N = 1595 cases had surgical source control within 48 h after onset of sepsis, of which 1563 (98%) cases had complete data on outcome and covariates for analysis. c Effect of time to antimicrobial therapy on the risk of progression to septic shock between 12 and 24 h after onset of sepsis. N = 1129 received their first antimicrobial treatment within 24 h after sepsis onset and were at risk of developing shock between 12 and 24 h, of these 1125 (99%) cases had complete data on outcome and covariates for analysis. d Effect of time to surgical source control on the risk of progression to septic shock between 12 and 24 h after onset of sepsis. Effect fitted by the fractional polynomial \({\left(\left(x+0.1\right)/10\right)}^{2}+{\left(\left(x+0.1\right)/10\right)}^{3}\) , where x is the timing of surgical source control. N = 193 cases did undergo a surgical source control within 24 h after sepsis onset and were at risk of developing shock between 12 and 24 h, of which 193 cases had complete data on outcome and covariates for analysis