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Effectiveness of Treatments for Severe Sepsis

A Prospective, Multicenter, Observational Study

¹ Critical Care Center, Hospital de Sabadell, CIBER Enfermedades Respiratorias, and ² Epidemiology and Assessment Unit, Instituto Universitario Fundación Parc Taulí, Universidad Autónoma de Barcelona, Sabadell, Spain; ³ Servicio de Medicina Intensiva, Hospital Infanta Leonor, Madrid, Spain; ⁴ Medical ICU, Rhode Island Hospital, Brown University School of Medicine, Providence, Rhode Island; ⁵ Servicio de Medicina Intensiva, Hospital Virgen de la Macarena, Sevilla; ⁶ Servicio de Medicina Intensiva, Hospital Universitari de Bellvitge, Hospitalet de Llobregat; and ⁷ Servicio de Medicina Intensiva, Hospital Universitari de Girona Doctor Josep Trueta, Girona, Spain

Correspondence and requests for reprints should be addressed to Ricard Ferrer, M.D., Critical Care Center, Hospital de Sabadell, Parc Taulí, 1 08208 Sabadell, Spain. E-mail: rferrer{at}tauli.cat

Rationale: Several Surviving Sepsis Campaign Guidelines recommendations are reevaluated.

Objectives: To analyze the effectiveness of treatments recommended in the sepsis guidelines.

Methods: 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.

Measurements and Main Results: 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.

Conclusions: 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.

Key Words: intensive care unit • guidelines • mortality • propensity scores

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Early appropriate antibiotic therapy, early goal-directed therapy, corticosteroids, recombinant human-activated protein C, tight glucose control, and lung protective strategies have been associated with survival benefits in patients with severe sepsis. What This Study Adds to the Field In a large cohort of ICU patients with severe sepsis, we found that two of the four treatments recommended in the Surviving Sepsis Campaign care bundles, i.e., early administration of broad-spectrum antibiotics and administration of drotrecogin alfa (activated), were independently associated with lower hospital mortality after adjusting for several independent clinical predictors of death.

 

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