Effectiveness of Treatments for Severe Sepsis: A Prospective, Multicenter, Observational Study

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Rationale</jats:title> <jats:p>Several Surviving Sepsis Campaign Guidelines recommendations are reevaluated.</jats:p> </jats:sec> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>To analyze the effectiveness of treatments recommended in the sepsis guidelines.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>In a prospective observational study, we studied all adult patients with severe sepsis from 77 intensive care units. We recorded compliance with four therapeutic goals (central venous pressure 8 mm Hg or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, central venous oxygen saturation 70% or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, blood glucose greater than or equal to the lower limit of normal but less than 150 mg/dl, and inspiratory plateau pressure less than 30 cm H2O for mechanically ventilated patients) and four treatments (early broad-spectrum antibiotics, fluid challenge in the event of hypotension and/or lactate greater than 36 mg/dl, low-dose steroids for septic shock, drotrecogin alfa [activated] for multiorgan failure). The primary outcome measure was hospital mortality. The effectiveness of each treatment was estimated using propensity scores.</jats:p> </jats:sec> <jats:sec> <jats:title>Measurements and Main Results</jats:title> <jats:p>Of 2,796 patients, 41.6% died before hospital discharge. Treatments associated with lower hospital mortality were early broad-spectrum antibiotic treatment (treatment within 1 hour vs. no treatment within first 6 hours of diagnosis; odds ratio, 0.67; 95% confidence interval, 0.50–0.90; P = 0.008) and drotrecogin alfa (activated) (odds ratio, 0.59; 95% confidence interval, 0.41–0.84; P = 0.004). Fluid challenge and low-dose steroids showed no benefits.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>In severe sepsis, early administration of broad-spectrum antibiotics in all patients and administration of drotrecogin alfa (activated) in the most severe patients reduce mortality.</jats:p> </jats:sec>